LCA Blog

Foundation Fighting Blindness Making $8.25 Million Investment in Gene Therapy Development

2011-12-07T21:47:00.001+01:00

November 23, 2011 - Recognizing the great potential of gene therapy for saving and restoring vision, the Foundation Fighting Blindness is investing an unprecedented $8.25 million for six new gene therapy research projects, all of which are targeted to have treatments ready for clinical trials within three years. These grants are allocated through the Foundation's Translational Research Acceleration Program, which funds research projects with strong, near-term clinical potential.

This focused drive to advance gene therapy will include funding potential treatments for: choroideremia, X-linked retinoschisis, retinitis pigmentosa (GUCYD2 mutations), two forms of Leber congenital amaurosis (GUCYD2 and RPGRIP1 mutations) and a nanoparticle gene delivery system that's useful for treating diseases caused by larger genes.

It was just three years ago that the Foundation Fighting Blindness reported outstanding results from its first gene therapy clinical trials: Young adults with virtually no vision could, for the first time, read several lines on an eye chart and navigate in dimly lit settings. Since then, more than 40 patients taking part in gene therapy clinical trials to treat a form of Leber congenital amaurosis (LCA) have benefited from this remarkable emerging treatment.

The success of those first LCA studies set the stage for rapid expansion in gene therapy development. In fact, by the end of this year, there will be human studies of gene therapies underway for as many as five retinal diseases, including the aforementioned LCA, wet age-related macular degeneration (AMD), Stargardt disease, Usher syndrome type 1B and autosomal recessive retinitis pigmentosa caused by mutations in the MERTK gene. These studies are independent of the six newly funded projects.

Virtually all of the Foundation's gene therapy work to date has focused on correcting specific genetic defects replacing bad genes with healthy genes that cause particular diseases. Through this new investment, some researchers are seeking less restrictive approaches to gene therapy that may apply to more than one disease.

"Gene therapy can do much more than we originally envisioned. We are now seeing it used to deliver vision-saving proteins, stop the growth of unhealthy blood vessels in wet AMD and even harness retinal cells other than photoreceptors for vision," says the Foundation's chief research officer, Dr. Stephen Rose. "These disease-independent initiatives have become an important part of our portfolio, because they can apply to people regardless of their defective gene."

For example, the Foundation is funding a collaboration of The Institut de la Vision in Paris and the Friedrich Miescher Institute in Basel, Switzerland, which is developing a gene therapy to resurrect and reactivate cone cells that are compromised by a wide range of diseases.

In many inherited retinal conditions, including retinitis pigmentosa, cones stop working before they completely degenerate. The research team's gene therapy revives degenerating cones, enabling them to regain their ability to respond to light and provide vision. The treatment also improves the health of cones and extends their lifespan significantly. Because cones provide central, daytime and detailed vision enabling someone to drive, read or see the faces of loved ones having the ability to resurrect them could mean a lot to someone who has a retinal disease.

With an increased investment in disease-independent treatments, like this one, coupled with numerous gene replacement therapies for specific diseases, the Foundation is building a strong gene therapy portfolio that may benefit people affected by a range of conditions.

Source http://www.blindness.org/index.php?option=com_content&view=article&id=2989:-foundation-making-825-million-investment-in-gene-therapy-development-&catid=294:foundation-news&Itemid=138

Potential clinical trial for LCA1!

2011-11-19T15:42:00.000+01:00

A clinical trial for LCA1 (Gucy2D mutations) might soon begin at Scheie Eye institute in Philadelphia!

To learn more and see if you can be a candidate, contact Dr. Jacobson (phone 215-662-9981, email jacobsos@mail.med.upenn.edu). He will first require the necessary medical records to be sent to him, then patients will be seen in Philadelphia for additional tests.

Study to Understand Leber Congenital Amaurosis (LCA) from Patients' and Parents' Perspectives

2011-10-06T23:08:00.001+02:00

Campbell Alliance is partnering with a pharmaceutical company that is currently developing a potential treatment for Leber Congenital Amaurosis (LCA), and would like to gain a deeper understanding of LCA from the perspectives of patients and parents. Through these perspectives, they can understand how to better educate the community about LCA.

They would like to conduct a 45-to-60 minute telephone discussion with interested LCA patients and parents of LCA children in order to capture their perspectives on living with LCA. Specifically, how has LCA changed your life and/or your child's life? What were your experiences receiving the diagnosis? How do you manage and address LCA on a daily basis, and where do you go for more information on the disease? For your time and insights, participants will receive a $100 honorarium.

They are conducting this research through October 20th and will close this study after the first 10 eligible patients respond. To qualify as a participant in this study, please contact Dr. Mary Lee (<mailto:mlee@campbellalliance.com>mlee@campbellalliance.com<mailto:mlee@campbellalliance.com>) with your responses to the below seven questions:

If you are a patient with LCA, please provide your responses to the below questions:

Have you been formally diagnosed with Leber Congenital Amaurosis (LCA) by a physician?

When did you receive your LCA diagnosis?

Are you willing to speak about your experiences being diagnosed with LCA, your day-to-day experiences living with LCA, and where you go for more information on LCA?

Are you fluent in English?

Are you over 18 years old?

What city, state, and country do you live in?

If you live in the US, are you willing to complete a W9 form (required by the IRS; we will not share your personal information with anyone) in order to receive your $100 honorarium?

If you are not a patient with LCA, please provide your responses to the below questions:

Are you a parent to a child who has been formally diagnosed with LCA by a physician?

How long ago did your child receive the LCA diagnosis?

Are you willing to speak about your experiences with your child's LCA diagnosis, your and your child's day-to-day experiences living with LCA, and where you go for more information on LCA?

Are you fluent in English?

Are you over 18 years old?

What city, state, and country do you live in?

If you live in the US, are you willing to complete a W9 form (required by the IRS; we will not share your personal information with anyone) in order to receive your $100 honorarium?

Please contact Dr. Mary Lee if you need additional information on this study.

Mary Lee PhD

Senior Consultant

Campbell Alliance

801 Gateway Boulevard

Suite 401

South San Francisco, CA 94080 USA

Voice: (650) 589-7400 x6138

Fax: (650) 589-7401

Cell: (626) 679-6712

An oral drug may treat some forms of LCA

2011-07-18T22:57:00.000+02:00

As already mentioned in this blog, an oral drug is being tested to treat some forms of LCA, and preliminary results have been astounding.

QLT is a Canadian company focused on developing innovative ocular products. QLT091001 is an oral synthetic retinoid proposed as a potential treatment for retinal diseases caused by gene mutations that interfere with the availability of 11-cis-retinal. Specifically, it is design to treat forms of Leber Congenital Amaurosis, and of RP. The forms of LCA the drug is targeting are those caused by mutations in LRAT (lecithin: retinol acyltransferase) and RPE65 (retinal pigment epithelium protein 65).

At the McGill University Health Centre of Montreal Children's Hospital, an early phase clinical trial is currently underway, to test safety and efficacy of QLT091001 in subjects with LCA due to RPE65 or LRAT gene mutations. Study participants are treated with oral QLT091001 daily for 7 days, and their visual function measured at predetermined time points after treatment, along with other physical and laboratory tests. To date, 9 subjects with LCA due to LRAT or RPE65 mutations have been enrolled. Preliminary results show improvements in best-corrected visual acuity and visual fields, which in some cases have persisted for up to 11 months beyond the end of treatment. Many subjects reported meaningful improvements in their activities of daily living. No serious adverse events occurred. These findings are very encouraging and indicate that seven days of oral QLT091001, generally well-tolerated, can produce rapid and sustained vision improvements, as well as subjective improvements in activities of daily living.

More LCA subjects are currently being enrolled; the results from patients in the LCA cohort are expected in the second quarter of 2011.

LCA, RP and the Visual Cycle

As mentioned above, QLT091001 is being developed for LCA and RP due to mutations in LRAT and RPE65. Mutations in LRAT and RPE65 result in the absence of 11-cis-retinal, an important molecule essential for vision. 11-cis-retinal is produced in the retinal pigment epithelium (RPE) and binds to the protein opsin to form rhodopsin in the rod outer segment.

Vision is initiated when a light photon is captured by 11-cis-retinal, resulting in isomerization to all-trans-retinal and dissociation from opsin. Vision is sustained by the cycling of all trans-retinal back into 11-cis-retinal, which occurs by a complex series of biochemical reactions involving multiple enzymes and proteins in the retinoid cycle.

How the Drug Works

The therapeutic strategy with QLT091001 is to facilitate recovery or restoration of visual function by acting as an analogue replacement for missing 11-cis-retinal and restoring the key biochemical component of the visual (retinoid) cycle. QLT091001 is an orally available synthetic prodrug that is converted to 9-cis-retinal, which forms the visual pigment isorhodopsin (instead of the usual rhodopsin formed from 11-cis-retinal). Isorhodopsin is a functionally active pigment in the visual cycle that undergoes conformational changes through the same photoproducts as 11-cis-retinal-regenerated rhodopsin.

In humans with a deficiency in 11-cis-retinal, isorhodopsin may act as a suitable substitute for rhodopsin in the visual cycle. This strategy proved successful in animal studies, as well as in humans, according to the preliminary findings of the Phase I clinical trial.

As with all drugs at the Phase I stage of development, these preliminary results need to be substantiated in larger safety and efficacy studies in the future.

To learn more, visit

http://www.clinicaltrials.gov/ct2/show/NCT01014052?term=qlt&rank=1

Gene therapy for GUCY2D works in mice, a human trial may be close!

2011-06-16T18:20:00.001+02:00

Researchers at the London's UCL Institute of Ophthalmology have demonstrated the efficacy of gene therapy in a mouse model of LCA 1, which is caused by mutations in the GUCY2D gene, the Gucy2e-/- mouse. a dose-dependent restoration of rod and cone function and an improvement in visual behaviour of the treated mice was observed, and the effects persisted up to 6 months post injection. These excellent results prompt the investigators to propose that a similar vector may be used in a clinical trial of gene therapy for LCA1!

Read the abstract at

http://www.ncbi.nlm.nih.gov/pubmed/21671801

Brain responds to vision even after prolonged visual deprivation

2011-05-31T22:41:00.000+02:00

In a paper just published in the Journal of Clinical Investigation, Ashtari et al. report the astonishing findings of their study on how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation, and provide the spectacular initial evidence that the visual cortex can be made responsive to visual input even after prolonged visual deprivation (up to 35 years. The research provides an excellent demonstration that gene augmentation therapy in humans with LCA2 rendered both the retina and the visual cortex far more sensitive to dimmer light and lower-contrast stimuli. The finding that the visual cortex can be reawakened after chronic visual deprivation in a rare eye disease may have much broader implications, providing promise for the outcome of gene therapy for both early- and late-onset retinal degenerative diseases.

You can read the abstract of the article at

http://www.ncbi.nlm.nih.gov/pubmed/21606598

From the Foundation Fighting Blindness: new RPE65 trial recruiting!

2011-05-14T12:24:00.000+02:00

Applied Genetic Technologies, the Oregon Health & Science University and the Foundation Fighting Blindness Announce Open Recruitment for a Phase 1/Phase 2 Research Clinical Trial

A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing RPE65 (rAAV2-CB-hRPE65) in Patients with Leber Congenital Amaurosis Type 2

Applied Genetic Technologies Corporation is the gene therapy development company providing the study drug and is the sponsor of this research trial. The Casey Eye Institute at the Oregon Health & Science University, Portland, OR (eIRB# 4892) is open for enrollment of patients in this clinical trial.

The RPE 65 gene makes the RPE65 protein that is needed for the retina to work normally. The study drug contains a normal copy of the RPE65 gene and also contains part of a virus called AAV. The AAV virus does not cause illness in humans, and it is used in the study drug to help the normal RPE65 gene get into cells of the retina after an eye surgeon injects the study drug beneath the retina in the back of one eye.

The purpose of this research study is to test whether the study drug, called rAAV2-CB-hRPE65, is safe and to see if it can improve vision in individuals who have a mutation in their RPE65 gene. Right now, rAAV2-CB-hRPE65 is not approved by the United States Food and Drug Administration (FDA) to treat people with changes in their RPE65 genes because not enough is known about the drug. The FDA will allow testing of the drug only in a research study such as this one.

Potential participants will be asked to come to the clinical site in Portland, Oregon. If their home is not close to the site, they will have to stay at a nearby hotel. During the first visit, there will be examinations and tests done to see if the individual is eligible to join the study. At the second visit, there will be more tests and if these results are acceptable, the participant will receive the study drug two days later. An eye surgeon will inject the study drug beneath the retina in one eye only.

After receiving the study drug, participants will be examined and have tests performed 1, 7 and 14 days later and then again at 1, 2, 3, 6, 9, 12, 18, and 24 months. Patients are expected to travel to the site where the injection was done for each of these visits, since special equipment is used to measure their visual function. After the 24-month visit, they will be contacted once a year for 15 years and asked to answer questions. They will also be asked to have a follow-up visit once a year from years 3 to 15 after treatment. These follow-up visits can be performed by their local ophthalmologist.

Participants are not paid for being in the study. However, participants will be reimbursed for reasonable costs related to the travel to attend the initial evaluation visit and, if accepted into the study, subsequent study visits.

Some of the basic criteria for inclusion or exclusion in this trial are as follows:

Inclusion Criteria

Retina disease consistent with a diagnosis of Leber Congenital Amaurosis caused by a documented mutation in the RPE65 gene;

At least 6 years of age;

Good general health;

Able to perform tests of visual and retinal function;

Visual acuity not better than 20/60 and not worse than hand motion in both the treated eye and the fellow eye

Exclusion Criteria

Pre-existing eye conditions that would preclude the planned surgery or interfere with interpretation of study endpoints or complications of surgery (e.g. glaucoma, corneal or lenticular opacities or history of retinal detachment)

History of immunodeficiency or other medical conditions that might increase the risk of study drug (rAAV2-CB-hRPE65) administration;

Use of anticoagulants or anti-platelet agents within 7 days prior to study agent administration

History of allergy or sensitivity to medications planned for use in the peri-operative period;

Use of any investigational agent or systemic corticosteroids or other immunosuppressive drug(s) within 3 months prior to enrollment.

Additional and detailed inclusion and exclusion criteria can be reviewed at www.clinicaltrials.gov. Study identifier is NCT00749957. Questions regarding criteria for possible participation can also be directed to the investigators at Casey Eye Institute.

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon, United States, 97239

Contact: Principal Investigator - J Timothy Stout, MD, PhD, MBA - 503-494-2435 - stoutt@ohsu.edu

Contact: Peter Francis, MD, PhD - (503) 418-1627 - francisp@ohsu.edu

Contact: Maureen Toomey, BS - (503) 494-3795 - toomeym@ohsu.edu

Applied Genetic Technologies Corporation www.agtc.com

Foundation Fighting Blindness www.FightBlindness.org

Gene therapy restores vision in fish model of CEP290 LCA and sheds light on CEP290 function!

2011-01-22T13:16:00.002+01:00

Researchers at the University of Iowa have created a zebrafish model of CEP290 LCA, and have been able to restore vision in these embryos by gene therapy! What's more, they showed that only a portion of the gene is enough to suppress the visual impairment. This is of the highest importance, because CEP290 is extremely large, and generating a vector capable of packaging such a large gene has been a challenge. The study by Baye et al, just published in Human Molecular Genetics, has thus shed light on the function of CEP290 specific regions.
The zebrafish is being widely used for research into vertebrate development and gene function. It offers several advantages to researchers, including a fully sequenced genetic code, well-understood and easily observable and testable developmental behaviors, availability of well-characterized mutants and rapid embryonic development.

The full article describing these crucial discoveries can be found online at
http://hmg.oxfordjournals.org/content/early/2011/01/21/hmg.ddr025.abstract

Treatment much closer for CEP290 and IQCB1 LCA!

2011-01-22T00:17:00.002+01:00

Patients affected by Leber's Congenital Amaurosis caused by either CEP290 or IQCB1, which are both ciliopathies, retain intact, though malfunctioning cones regardless of the degree of vision loss, even in adulthood! This had been already shown for CEP290 and has now been confirmed also for IQCB1.
An animal model sufficiently similar to human disease is essential for preclinical testing of any therapy before it is tried on man. Naturally occurring animal models with CEP290 mutations exist, namely the RD16 mouse and the Abyssinian cat. Both are good models but their phenotypes are different from those of human patients. Now a new animal model has been created which closely mimics the human phenotype! It is called the

rd16;Nrl mouse, generated by crossing RD16 mice with Nrl ^{mice. This double-mutant mouse shows substantially retained cone photoreceptors, with}

^{disproportionate cone function loss, like the human disease.}

A new study by Dr. Arthur Cideciyan and colleagues, just published online in Human Molecular Genetics, highlights the astounding survival of cones in the retinas of patients with these 2 forms of LCA across a wide age spectrum, and presents the characteristics of this new animal model which will greatly contribute to expedite preclinical research towards gene therapy trials in man!

You can read the paper's abstract at

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=21068128

CEP290 is a strong candidate for gene therapy!

2010-11-14T11:25:00.000+01:00

Research on CEP290 continues to thrive, and knowledge on its function is pouring in. The latest findings are summarized in a paper by Betleja & Cole, just published in Current Biology. They discuss the most recent discovery, reported by Craige et al in an article published in September in the Journal of Cell Biology, which indicates the role of CEP290 as a gatekeeper within the cell. Basically, it will determine which substances can transfer between the inner and outer regions of the cell. When the gene is mutated, the correct transfer of proteins is disrupted, so that abnormal accumulation of certain proteins and reduction of others can occur. It is likely that different CEP290 mutations will disrupt the transport of different proteins, thus explaining the large spectrum of disorders associated with CEP290 (from isolated blindness to complex syndromes affecting multiple organs).

Craige et al also showed that CEP290 is a dynamic component of the cell's cilia, that can shuttle between the inner and outer regions of the cell and rescue transport. This makes it a strong candidate for gene therapy!

I'm not a geneticist, this is what I could understand from the article in plain terms. The Full text of the paper by Betleja & Cole is available free at

http://www.cell.com/current-biology/fulltext/S0960-9822(10)01215-7#MainText

The abstract of the work by Craige et al can be found here

http://www.ncbi.nlm.nih.gov/pubmed/20819941

This is very good news

Fran

Gene therapy proven effective in the Guanylate Cyclase-1 Mouse

2010-07-02T14:44:00.002+02:00

This has just been published. Here is the link to the abstract in Medline. Great news for LCA 1 and LCA in general!
http://www.ncbi.nlm.nih.gov/pubmed/20593011

Highlights from the 16th Retina International Conference

2010-06-29T21:13:00.002+02:00

Hi all,
at the 11th hour I decided to attend the 16th Retina International conference, held in Stresa, Italy, last weekend. So glad I did! I've written down some of the highlights that most impressed me. The conference wasn't specifically on LCA but most of the LCA researchers we know were there, so that was a terrific opportunity for me. Here is some of the best stuff:

Dr. Jean Bennett presented the astounding results of the RPE65 trials. Children who were virtually blind can now play baseball and walk without a cane! We all had read that, but to hear it from her was exciting.

Dr. Koenekoop showed the incredible results of the QLT drug for LRAT LCA. After only nine days of oral administration, vision improved dramatically, and the visual field kept increasing until it tripled! It produced improvements even in an adult patient. He said they will now test it on people with RPE65. To the question about future application of similar drugs to different LCA genes, he did not rule it out, but didn't go into details.

Many researchers said that soon gene therapy trials for other genes will be planned. Dr. Jean Bennett said that she cannot say which will come next, but different labs are working on diferent animal models. Some of the candidates for future clinical trials that were mentioned were AIPL1, LCA5, RPGRIP, Gucy2d, and CEP290. CEP290 is being studied a lot, the problem with it is that it is a large gene, but many labs are working on building the right vector to get it into the retina; once it is found, things should go fast from mice to cats to humans. I was lucky to be able to speak with Dr. Koenekoop and Dr. Auricchio about CEP290, they both sounded quite optimistic.

Dr. Eberhard Zrenner spoke about the retina prosthesis. It's promising, though the visual field it allows is still pretty small. We were shown a video where a blind person receiving the implant was able to read a few letters on a chart and recognize some objects. For now they will not try it on people blind from birth.

Unfortunately I missed the lecture on stem cells by Robert Ali. Comments I heard were that research is progressing, but application is a bit further away.

An exciting new development I had never heard about before is photoswitch, which is a strategy that aims to activate ganglian cells of the retina to interpret light and send signals to the brain, bypassing photoreceptors. It isn't working yet, but Dr. Gerald Chader was confident that it might work soon, and make it to human trials. This is wonderful as it would enable vision even in people with no living photoreceptors.

A lot was said about drugs like nerve growth factors which can prolong the life of photoreceptors, but I didn't follow those too closely, sorry.

All in all it was a thrilling experience, lots of good news, good pespectives for the future, an an optimistic atmosphere, as well as lots of wonderful researchers who were all willing to answer our questions.

If you have any questions, please email them to me and I'll see if I can remember more...

Fran

Fw: Vote FRR @APX Gives Back...60 more day to go!

2010-06-22T20:58:00.002+02:00

Dear Friends, 60 more days

FRR is so appreciative of being one of the 75 charities to have the opportunity to win $100,000 through APX Gives Back!

We have 60 more days to VOTE DAILY! So please pass along the information to your friends and family.

Think about it, every email you send also helps raise awareness of Retinal Degenerative Disease.

FRR needs your daily endorsements through Saturday, August 21.

Here's the info:

1. Go to: http://apps.facebook.com/apxgivesback
2. Enter in search field "The Foundation for Retinal Research" in the Central Region
4. Click "Vote this charity"
5. Share the email with your friends and family
6. PLEASE VOTE DAILY between NOW and Saturday, August 21

To learn more about APX Alarm and the APX Givesback Project go to:
http://www.apxgivesback.com/the-apx-givesback-project/

To learn more about the Foundation for Retinal Research go to: TFRR.ORG

Thank you for your support and for spreading the word,

Foundation for Retinal Research

For questions, please contact:
Julie Levine Rubin
Development Director
Foundation for Retinal Research
E-mail: julie@tfrr.org

Mailing Address:
Foundation for Retinal Research
666 DundeeRoad #1104
Northbrook, IL 60035
US

Contact Name: Julie Levine Rubin
Telephone Number: 847.224.5085

Recent breakthroughs in research

2010-04-25T15:52:00.003+02:00

Hello, I'm sorry I have not updated this blog regularly lately, due to family problems that have kept my attention away from LCA research, which fortunately kept making progress even while I was absorbed by other things...of course.

There are two exciting developing stories I'm happy to share:

oral treatment for LCA caused by the LRAT gene has proven effective in early studies. Researchers are now planning to enrol patients with RPE65 mutations as well.
You can read the full story here

http://www.osnsupersite.com/view.aspx?rid=63449

Also, a study on mice carrying mutations in the RPGRIP1 gene, published in Human Gene Therapy, has shown that gene therapy can slow photoreceptor degeneration, laying the basis for human trials for LCA caused by RPGRIP1, also having therapeutic implications for other forms of LCA linked to ciliary defects.
You can read the abstract here

http://www.ncbi.nlm.nih.gov/pubmed/20384479

Glad I could share some good news!

Fran

Gene therapy works on AIPL1 mice

2009-08-29T10:30:00.001+02:00

I'm sorry this blog hasn't been updated in a while. Now though there is
finally exciting news to share. A study has just been publish demonstrating
that gene therapy works in mous models of LCA caused by mutations in the
AIPL1 gene! The conclusions of the authors are very encouraging, as they
recommend the technique to be used in human trials!

AIPL1 is the 4th gene for which gene therapy has been shown to work,
together with RPE65 (for which studies are continuing and growing on
humans!) and Gucy2D and RPGRIP on animals.

Here is the abstract from Medline

Fran

Gene Ther. 2009 Aug 27. [Epub ahead of print]
Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations.
Sun X, Pawlyk B, Xu X, Liu X, Bulgakov OV, Adamian M, Sandberg MA, Khani SC, Tan MH, Smith AJ, Ali RR, Li T.
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is required for the biosynthesis of photoreceptor phosphodiesterase (PDE). Gene defects in AIPL1 cause a heterogeneous set of conditions ranging from Leber's congenital amaurosis (LCA), the severest form of early-onset retinal degeneration, to milder forms such as retinitis pigmentosa (RP) and cone-rod dystrophy. In mice, null and hypomorphic alleles cause retinal degeneration similar to human LCA and RP, respectively. Thus these mouse models represent two ends of the disease spectrum associated with AIPL1 gene defects in humans. We evaluated whether adeno-associated virus (AAV)-mediated gene replacement therapy in these models could restore PDE biosynthesis in rods and cones and thereby improve photoreceptor survival. We validated the efficacy of human AIPL1 (isoform 1) replacement gene controlled by a promoter derived from the human rhodopsin kinase (RK) gene, which is active in both rods and cones. We found substantial and long-term rescue of the disease phenotype as a result of transgene expression. This is the first gene therapy study in which both rods and cones were targeted successfully with a single photoreceptor-specific promoter. We propose that the vector and construct design used in this study could serve as a prototype for a human clinical trial.

PMID: 19710705 [PubMed - as supplied by publisher]

Anche quest'anno il 5 per mille alla IALCA

2009-03-19T21:53:00.003+01:00

Ormai è tempo di dichiarazione dei redditi...Anche quest'anno, per gli italiani, non dimenticate di assegnare il 5 per mille alla IALCA, Associazione Italiana LCA. Come scrive il Presidente Nicola Stilla "...donare il 5 per mille della propria dichiarazione dei redditi a IALCA è uno dei modi più facili, economici ma estremamente efficaci per aiutare l'Associazione. Infatti NON COSTA ASSOLUTAMENTE NULLA, basta semplicemente mettere una firma nello spazio dedicato sul modulo per la dichiarazione dei redditi e riportare il codice fiscale della IALCA che è il seguente: 96036310181"

Grazie

Francesca

15th LCA gene identified!

2009-03-09T18:38:00.003+01:00

Dr. Robert Koenekoop of Montreal Children's hospital did it again. For the third time, his team has discovered a gene which, when mutated, can lead to Leber's Congenital Amaurosis. First came CEP290 in 2006, then LCA5 followed just one year later. Now it's the turn of SPATA7. Mutations in this gene disrupt the protein transport between two important compartments of the cell: the endoplasmic reticulum and the Golgi apparatus. All proteins in every cell have to pass through this transport pathway; thus SPATA7 plays a major role in vision.

Read more on this breaking news in the MUHC release
http://www.muhc.ca/media/news/item/?item_id=104925

Stem cell therapy restores some visual function in crx-deficient mice

2009-01-09T19:11:00.005+01:00

1: Cell Stem Cell. 2009 Jan 9;4(1):73-9.

Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in crx-deficient mice.

Lamba DA, Gust J, Reh TA.

Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
Some of the most common causes of blindness involve the degeneration of photoreceptors in the neural retina; photoreceptor replacement therapy might restore some vision in these individuals. Embryonic stem cells (ESCs) could, in principle, provide a source of photoreceptors to repair the retina. We have previously shown that retinal progenitors can be efficiently derived from human ESCs. We now show that retinal cells derived from human ESCs will migrate into mouse retinas following intraocular injection, settle into the appropriate layers, and express markers for differentiated cells, including both rod and cone photoreceptor cells. After transplantation of the cells into the subretinal space of adult Crx(-/-) mice (a model of Leber's Congenital Amaurosis), the hESC-derived retinal cells differentiate into functional photoreceptors and restore light responses to the animals. These results demonstrate that hESCs can, in principle, be used for photoreceptor replacement therapies.

PMID: 19128794 [PubMed - in process]

www.ncbi.nlm.nih.gov

Project 290 aims to find cure for CEP290 LCA!

2008-12-28T12:12:00.003+01:00

Ten Teams from among the best american Universities and laboratories are uniting forces to fight LCA caused by CEP290. This is happening mostly thanks to the generosity of Boston Celtics owner Wyc Grousbeck - whose teenage son, Campbell, has LCA - who has donated a huge sum specifically for this purpose. This multidisciplinary team is embarking on a road of exploration which, hopefully, will lead to cures in humans in the near future. This is overwhelming news for those of us whose lives have been affected by CEP290 mutations, and adds to the equally thrilling news of the considerable funds obtained by Canadian researchers who are pursuing the same goal.

Here is the list of researchers involved in Project 290. Links are provided for each researcher, to learn more about each lab’s research area and role in the project.

Dr. Jean Bennett
University of Pennsylvania, Children's Hospital of Philadelphia

Dr. Elias Traboulsi
Cleveland Clinic’s Cole Eye Institute

Dr. Leonard Zon
University of Harvard

Dr. Richard Weleber
Oregon health & Science University

Dr. Samuel Jacobson
University of Pennsylvania, Scheie Eye Institute

Dr. Jerry Fishman
University of Illinois at Chicago

Dr. Edwin Stone
University of Iowa, Carver Laboratory for Molecular Diagnosis

Dr. George Witman
University of Massachusetts

Dr. Kristina Narfstrom
University of missouri at Columbia

Dr. Joel Rosenbaum
Yale University

To donate to Project 290, please contact Shannon Thomas at 515-450-7788, or at
shannon-thomas@uiowa.edu

If you’d like to drop a message of thanks and support to Wyc Grousbeck, just visit the Boston Celtics web site
http://www.nba.com/celtics/

To read about the Grousbeck’s incredible story, visit
http://sports.espn.go.com/nba/columns/story?id=3399631

This news was a wonderful Christmas gift, and a great way to head into the new year. Many thanks to my friend Jennifer for gathering all this precious information.

Happy new year to everyone!

Fran

Huge research grant to fight LCA

2008-12-11T22:19:00.002+01:00

We recently learned that five Canadian and American teams, among which Dr. Koenekoop's from Montreal, had obtained a 2.4 million dollar grant from the Canadian Institutes of Health Research (CIHR) and the Foundation Fighting Blindness Canada (FFB), to research gene therapy for number of retinal diseases, including Leber Congenital Amaurosis. That was exciting enough, but today it has been reported that the grant is actually larger, amounting to 3 million dollars!!

The project on LCA will last five years, and has the ambitious goals to develop gene therapy for other types of LCA, after the RPE65 trial success. As far as I know, the focus will be on the CEP290 gene, LCA10, which is the main cause of Leber's. This part of the project will begin with research on the RD16 mouse and the Abyssinian cat (naturally occurring animal models of CEP290 LCA), and finally, if all goes well, on humans!!

Here are a couple of links to learn more

http://www.mcgill.ca/newsroom/news/item/?item_id=103088

http://www.gtamotorcycle.com/vbforum/showthread.php?p=770014#post770014

Some cool stuff on trials for Leber's Congenital Amaurosis

2008-10-18T10:33:00.004+02:00

I've found some excellent documentaries that will make our day. Read about the UK RPE65 clinical trial and hear Prof. Robert Ali's words on the future of gene therapy for retinal disorders on the Telegraph website

http://www.telegraph.co.uk/earth/main.jhtml?view=DETAILS&grid=&xml=/earth/2008/09/22/scieye122.xml

Watch the astounding improvement of Manuela after gene therapy for RPE65 in the American-Italian trial, and hear from Dr. Maguire and Dr. Jean Bennett
on ABC

http://abcnews.go.com/Video/playerIndex?id=4736538&affil=wmar

Phase I study of oral drug for RPE65 LCA

2008-10-09T21:18:00.003+02:00

QLT announces the initiation of a Phase I trial of its synthetic retinoid product VANCOUVER, Oct. 9 /CNW/ - QLT Inc. (NASDAQ: QLTI; TSX: QLT) announced today that it has initiated a Phase I safety study in healthy adults of QLT091001, an orally administered synthetic retinoid replacement therapy for 11-cis-retinal, which is a key biochemical component of the visual retinoid cycle. The drug is being developed for the potential treatment of Leber's Congenital Amourosis (LCA), an inherited progressive retinal degenerative disease that leads to retinal dysfunction and visual impairment beginning at birth.The Phase I study is an open-label, single center, ascending dose trial that will determine the safety and tolerance of multiple administrations of the synthetic retinoid drug in approximately 18 healthy adult volunteers.Participants will be enrolled in up to 6 cohorts of increasing doses."We believe our retinoid synthetic drug program is a very interesting opportunity as there are no currently available treatments for patients with LCA, which affects one in one-hundred thousand newborns world-wide," said Bob Butchofsky, President and Chief Executive Officer of QLT. "This program also supports the Company's new ocular focus and we look forward to reporting the Phase I data in the first half of 2009. We hope that our findings will support further clinical studies in this orphan indication."

About Synthetic Retinoid Drugs

Genetic diseases in the eye such as Leber's Congenital Amaurosis (LCA)and Retinitis Pigmentosa (RP) arise from gene mutations of enzymes or proteins required in the biochemistry of vision. QLT091001 is a replacement for 11-cis-retinal which is an essential component of the retinoid-rhodopsin cycle and visual function. Two different gene mutations (Retinal pigment epithelium protein 65 (RPE65) and lecithin-retinol acyltransferase (LRAT)) result in an inadequate production of 11-cis-retinal and occur in approximately 10% of patients with LCA and to a lesser extent in RP.The basis for using synthetic retinoids as replacement therapy for conditions where genetic defects result in deficiency of 11-cis-retinal is founded on experiments in mouse genetic models. These experiments used mice that have mutations in either the RPE65 or LRAT genes, the same as those associated with LCA in humans. Both mouse models have clinical features of the human disease. The biological activity of the synthetic retinoid was monitored by measuring the level of pigment-related compounds in the eye. Retinal function was also assessed by detecting electroretinograms (ERGs), electrical nerve signals from the retina. Oral administration of QLT091001 showedevidence of having corrected the biochemical defect in the retinoid cycle in light-sensing cells (rods) and appeared to restore ERG responses to light in both models of LCA.

About QLT

QLT Inc. is a global biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapies. Our research and development efforts are focused on pharmaceutical products in the fields of ophthalmology and dermatology. In addition, we utilize three unique technology platforms, photodynamic therapy, Atrigel(R) and punctal plugs with drugs, to create products such as Visudyne(R) and Eligard(R) and future product opportunities. For more information, visit our web site at
www.qltinc.com.

In April of 2006, QLT entered into an exclusive worldwide co-development and licensing agreement with Retinagenix, LLC, to develop active synthetic retinoid products for the treatment of degenerative retinal diseases.Pre-clinical studies have demonstrated that orally administered synthetic retinoid drugs cause long-lasting restoration of retinal function. Under the terms of the agreement, QLT is responsible to develop and commercialize the products for use in ocular and all other human diseases.

Story taken from

http://www.newswire.ca/en/releases/archive/October2008/09/c4584.html

2008 LCA Conference Scientific Sessions

2008-07-19T18:21:00.003+02:00

The 2008 LCA conference is here! Take a look at the scientific schedule to
have in idea of the wealth of information that will come out of the
conference.
I hope a DVD will be made available for those who cannot attend, like it was
done in 2006. Thanks to the folks at the Foundation for Retinal Research for
making this possible!

Fran

Saturday, July 26, 2008
FRR-LCA Family Conference - SCIENTIFIC SESSIONS

INTRODUCTION

8:30 - 8:40 am Welcoming and Opening Remarks - David Brint, Dr. Joe
Hollyfield

SESSION I: LCA CHARACTERISTICS: PHENOTYPES AND GENOTYPES
Moderator: Dr. Elias Traboulsi

8:40 - 9:00 am Phenotype-Genotype Relations: An Overview - Dr.
Elise Heon
9:00 - 9:25 Project 3000 - Dr. Ed Stone
9:25 - 9:45 LCA in Adults - Dr. Elias I. Traboulsi
9:45 - 10:00 Question & Answer Session - Drs. Heon, Stone,
Traboulsi

10:00 - 10:15 Break

SESSION II: LCA GENES
Moderator: Dr. Ed Stone

10:15 - 10:25 am LCA Genes: An Overview - Dr. Jerry Chader
10:25 - 10:50 RPGRIP Gene, CEP290 & LCA5 - Dr. Tiansen Li
10:50 - 11:10 The RPE65 Gene - Dr. Michael Redmond
11:10 - 11:20 Question & Answer Session- Drs. Li, Redmond and
Chader

11:20 - 12:20 Lunch

SESSION III: LCA THERAPIES
Moderator: Dr. Elise Heon

12:20 - 12:30 pm LCA Therapies - An Overview - Dr. Jerry Chader
12:30 - 12:55 Gene Therapy - Dr. Jean Bennett
12:55 - 1:20 Stem Cell Technologies - Dr. Michael Young
1:20 - 1:45 Pharmaceutical Therapy - Dr. Krzysztof
Palczewski
1:45 - 2:10 Retinal Electronic Prostheses - Dr. Mark
Humayun
2:10 - 2:35 Questions & Answers - Dr. Bennett, Young,
Humayun and Drs. Chader, Palcewski

2:35 - 2:50 Break

SESSION IV: LCA THERAPIES - 2
Moderator: Dr. Joe Hollyfield

2:50 - 3:15 Nanotechnology Applications to LCA - Dr. Muna
Naash
3:15 - 3:35 Encapsulated Cell Technology - Mr. Konrad
Kauper
3:35 - 4:00 NEI Resources for LCA Research - Dr. Neeraj
Agarwal
4:00 - 4:25 Question & Answer Sessions - Drs. Naash,
Agarwal and Mr. Kauper
4:25 - 4:40 General Questions & Discussion - Drs. Chader,
Hollyfield and Traboulsi
4:40 - 4:45 0 Concluding Statements and Adjournment - Mr.
and Mrs. Brint

Make a difference in retinal research without spending a dollar

2008-06-10T23:40:00.001+02:00

Message from the Foundation Fighting Blindness

Hello,
We have some great news! RCause.org has selected the Foundation Fighting Blindness as its charity of the month.

Just by clicking on the link provided, you can contribute to the Foundation Fighting Blindness…for free. In fact, the donations are paid for by the advertisers.

Make sure to tell your friends and family to visit RCause.org! Each time a visitor clicks on our logo, we receive more money to fund the critical research that will one day cure retinal degenerative diseases. Please be sure to visit
http://www.rcause.org/
as often as you can. Not only will you support FFB by clicking on our logo, but you can also enter a raffle drawing for a chance to win money.

This is a win-win situation for you and the Foundation, so please visit
http://www.rcause.org/
as many times as you can during the month of June!

Thank you,

Foundation Fighting Blindness
11435 Cronhill Drive, Owings Mills, MD 21117
800-683-5555
www.FightBlindness.org

Gene therapy safety and success proven once again

2008-05-04T19:54:00.002+02:00

The news just came in. A third gene therapy trial for Leber Congenital Amaurosis caused by mutations in RPE65, carried out at the University of Florida, has proven safe, and has led to improvement of vision in 4 out of the 6 participants. Only a few days ago, the world of science was shaken by similar results obtained by 2 analogous trials conducted in London and in the US (see previous posts).

More to come for sure!

Message from David Brint, President of FRR

2008-05-01T23:41:00.001+02:00

Dear Friends:
As some of you may have heard, Jean Bennett at the Children's Hospital of Philadelphia has announced the initial results of the RPE 65 gene therapy trial. Jean has reported that all three of the injected patients have had some restored vision. This includes vision of up to three lines on an eye chart andimproved ambulatory vision.
This is the most significant result for the restoration of sight in history.
You all should know that the current trial is only a safety trial and has only included a half dose of the gene. What this all means is that the gene vectoris not causing any health problems to date and that the results may improve with increased dosing.
Gene therapy will be a potential treatment for all forms of LCA where photoreceptors are intact.
The FRR has been a supporter of Jean Bennett's work and we are proud of her team's accomplishment.
The attached web links will give you more information
http://abcnews.go.com/Health/wireStory?id=4737873 http://content.nejm.org/cgi/content/full/NEJMoa0802268
Sincerely,
David Brint
President FRR

Clinical trial recap

2008-04-29T22:44:00.003+02:00

So after the initial chaotic excitement, let us try to recap:
two separate gene therapy trials for RPE65 LCA proved the treatment is safe and can work. One was carried out in England, at Moorfields Eye Hospital and the University College London, the other at the Children’s Hospital of Philadelphia in collaboration with The University of Pennsylvania, the Seconda Università of Naples and the Telethon Institute of Genetics and Medicine, also of Naples - go Italy!
Both trials enrolled three patients. The treatment proved safe for all six patients, and it improved vision in all three subjects in the Italian/US trial and in 1 of the London trial.

Both papers were published in the New England Journal of Medicine on the same day. Here are the links to the articles’ abstracts

London trial

US/Italian trial

Certainly a lot to absorb, but the message is simple: the road to future trials for Leber's Congenital Amaurosis and other retinal genetic disorders is now open!

Italian/US LCA gene therapy trial also successful!!

2008-04-28T20:46:00.001+02:00

Gene therapy improves vision in patients with congenital retinal disease

Patients' vision improved from detecting hand movements to reading lines on eye chart

In a clinical trial at The Children’s Hospital of Philadelphia, researchers from The University of Pennsylvania have used gene therapy to safely restore
vision in three young adults with a rare form of congenital blindness. Although the patients have not achieved normal eyesight, the preliminary results
set the stage for further studies of an innovative treatment for this and possibly other retinal diseases.

An international team led by The University of Pennsylvania, The Children’s Hospital of Philadelphia, the Second University of Naples and the Telethon Institute
of Genetics and Medicine (both in Italy), and several other American institutions reported their findings today in an online article in the New England
Journal of Medicine.

“This is the first gene therapy trial for a nonlethal pediatric condition,” said Albert M. Maguire, M.D., Associate Professor, Department of Ophthalmology,
University of Pennsylvania School of Medicine and a physician at The Children’s Hospital of Philadelphia. Maguire, together with his wife, Jean Bennett,
M.D., Ph.D., Professor of Ophthalmology at Penn and Senior Investigator at the F.M. Kirby Center for Molecular Ophthalmology at Penn’s Scheie Eye Institute,
have been researching inherited retinal degenerations such as Leber congenital amaurosis (LCA), for 18 years. LCA is a group of inherited blinding diseases
that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness during a patient’s twenties
or thirties. Currently, there is no treatment for LCA.

“Patients’ vision improved from detecting hand movements to reading lines on an eye chart,” Maguire added. In 2001, Bennett and Maguire were part of a team
which reported successfully reversing blindness using gene therapy on dogs affected by the same naturally occurring form of congenital blindness.

The current study is sponsored by the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia, directed by Katherine A.
High, M.D. High, a study leader and an Investigator of the Howard Hughes Medical Institute, has been a pioneer in translational and clinical studies of
gene therapy for genetic disease, and in 2005 initiated a collaboration with Bennett and her group to translate their exciting animal findings into a clinical
study.

The scientists used a vector, a genetically engineered adeno-associated virus, to carry a normal version of the gene, called RPE65, that is mutated in one
form of LCA. Three patients, ages 19, 26 and 26, received the gene therapy via a surgical procedure performed by Maguire between October 2007 and January
2008 at The Children’s Hospital of Philadelphia, where the gene vector was manufactured at the hospital’s Center for Cellular and Molecular Therapeutics
(CCMT).

Starting two weeks after the injections, all three patients reported improved vision in the injected eye. “Standard vision tests showed significantly improved
vision in the patients,” said Alberto Auricchio, M.D., a study leader from the Telethon Institute of Genetics and Medicine and University of Naples Federico
II. The researchers also reported that each injected eye became approximately three times more sensitive to light, and each was improved compared to the
uninjected, previously better functioning eye.

The LCA gene therapy vector showed no signs of causing inflammation in the retina or other toxic side effects. One of the three patients had an adverse
event, a hole in the retina that did not affect eyesight and may have been surgery-related, rather than related to biological effects of the therapeutic
gene or the vector used to carry it.

The patients enrolled in the study to date were identified at the Department of Ophthalmology at the Second University of Naples, an institution with long-standing
experience in collecting and studying patients with inherited retinal diseases, under the supervision of Francesca Simonelli, M.D.

Testing continued over a period of six months following the gene therapy vector administration. One patient was better able to navigate an obstacle course
compared to before the injection. The patients also had less nystagmus, an involuntary movement of the eyes that is common in LCA. In the patient who experienced
better vision even in the uninjected eye, the researchers suggest that the reduced nystagmus benefited both eyes.

“The current clinical trial will continue with more patients and with ongoing follow-up to monitor results,” said Bennett. “We expect improvements to be
more pronounced if treatment occurs in childhood, before the disease progresses.”

“This result is important for the entire field of gene therapy,” notes High, a past president of the American Society of Gene Therapy. “Gene transfer has
been in clinical trials for over 15 years now, and although it has an excellent safety record, examples of therapeutic effect are still relatively few.
The results in this study provide objective evidence of improvement in the ability to perceive light, and thus lay the groundwork for future studies in
this and other retinal disorders,” said High.

The pace of moving from pre-clinical discoveries into clinical trials has typically been slow in the field of gene therapy due to the breadth of expertise
required, ranging from in-depth knowledge of the disorder to detailed understanding of vector design, manufacture, and pre-clinical evaluation. The complexities
of regulatory oversight at both the federal and local levels also present challenges. Through the Center for Cellular and Molecular Therapeutics, The Children’s
Hospital of Philadelphia has developed concentrated expertise and substantial resources to facilitate the “bench to bedside” translation of gene therapy.

###

The scientists at the Clinical Vector Core at CCMT have over 30 years experience in the biopharmaceutical industry and in 2007 were awarded a National Institutes
of Health contract for clinical grade vector production for trials throughout the United States, attesting to the quality of their vector manufacture.
The CCMT’s dedicated regulatory affairs support has specialized expertise in clinical gene therapy and coordinates trial approvals from multiple scientific
and ethic review committees, manages the study activities at all clinical sites, and ensures compliance with international quality standards for conducting,
monitoring, and reporting clinical trials.

The clinical trial was sponsored and primarily funded by the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia.
Research support was received from The Department of Ophthalmology at the University of Pennsylvania, the F.M. Kirby Foundation, the Foundation Fighting
Blindness, Research to Prevent Blindness, the Macula Vision Foundation, the Paul and Evanina Mackall Foundation Trust at the Scheie Eye Institute, the
Rosanne H. Silbermann Foundation, the Italian Telethon Foundation, the Associazione Italiana Amaurosi Congenita di Leber, the National Center for Research
Resources, the Howard Hughes Medical Institute, the National Eye Institute of the National Institutes of Health, private philanthropy, and an anonymous
donor who is committed to advancing pediatric medicine through maximizing the potential of gene therapy.

About The Children’s Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through
its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major
research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among
the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs
have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit
http://www.chop.edu.

About the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia: The Center for Cellular and Molecular Therapeutics
was established in 2005, with a mission of fostering a multidisciplinary approach to the development of new cell and gene therapies for the treatment of
serious and debilitating childhood disorders. The Center conducts cutting edge research in gene transfer, gene regulation, gene discovery, stem cell biology,
experimental models of disease, and correction of genetic disease. Consistent with Children’s Hospital’s research mission to transform scientific insights
into improved medical therapies, the Center has the capacity to support rapid translation of promising results from the laboratory to the clinic, through
facilities for manufacturing clinical-grade gene therapy vectors for clinical studies, and through specialized regulatory support for the design and implementation
of clinical trials of complex, novel classes of therapeutics.

About The University of Pennsylvania School of Medicine’s Department of Ophthalmology and The Scheie Eye Institute: Scheie Eye Institute is the Department
of Ophthalmology at the University of Pennsylvania. Its ten clinical divisions include the Division of Pediatric Ophthalmology which is housed at The Children’s
Hospital of Philadelphia. The Department of Ophthalmology (
http://www.uphs.upenn.edu/ophthalmology)
is also home to the F.M. Kirby Center for Molecular Ophthalmology, founded in 1994 with a generous gift from the F.M. Kirby Foundation, which has provided
continuous support for the ongoing research for the past 14 years. The F.M. Kirby Center was the first molecular biology center devoted to developing gene
therapy for hereditary causes of vision loss. The Center serves as home to the laboratories of seven investigators who conduct research on the cellular
and molecular biology of eye disease and visual function. Current studies in the F.M. Kirby Center include evaluations of the molecular genetics and pathogenetic
mechanisms involved in optic nerve disease and inherited retinal and macular degenerations, cell biology studies of photoreceptor sensory cilia, delineation
of mechanisms underlying the light responses of rods and cones, gene discovery of complex and monogenic disorders, development of methods with which to
non-invasively monitor retinal and visual function in animal models and humans, and design of novel methods with which to image retinal cells. (
http://www.uphs.upenn.edu/news)

The Department of Ophthalmology (Scheie Eye Institute) at Penn is a world leader in patient care and eye and vision research. In 2006, the most recent year
for which published data are available, Scheie Eye Institute was the #1 recipient of eye research funds from the National Eye Institute, National Institutes
of Health among all departments of ophthalmology in the United States. Currently the National Eye Institute is funding a 46-site randomized clinical trial
to evaluate treatment strategies for age-related macular degeneration coordinated by faculty at Scheie Eye Institute at Penn.

About The Telethon Institute of Genetics and Medicine (TIGEM): TIGEM is a local and international reference for research on human genetic diseases. It was
created in 1994 by the Telethon Foundation, one of Italy's major non-profit organizations, to promote the advancement of research aimed at the diagnosis,
cure and prevention of human genetic diseases. TIGEM's mission is to understand the mechanisms of genetic diseases and to develop preventive and therapeutic
strategies. Since its establishment, the Institute has grown considerably. It now consists of a large fully refurbished site, and comprises 13 independent
research groups with over 170 members including graduate students, postdoctorate fellows, technicians and administration. The scope of the science currently
covered at TIGEM spans three disease research area: developmental disorders, inborn errors of metabolism and inherited eye diseases. Research approaches
include cell biology, functional genomics, systems biology and gene therapy. TIGEM offers training programs in medical and human genetics, in cooperation
with local and international universities such as the British Open University. Research activity at TIGEM is supported by core facilities dedicated to
providing state-of-the-art technology as well as housekeeping assistance.

About the Howard Hughes Medical Institute (HHMI): HHMI, a non-profit medical research organization that ranks as one of the nation's largest philanthropies,
plays a powerful role in advancing biomedical research and science education in the U.S. In the past two decades HHMI has made investments of more than
$8.3 billion for the support, training, and education of the nation's most creative and promising scientists. HHMI's flagship program in biomedical research
rests on the conviction that scientists of exceptional talent, commitment, and imagination will make fundamental biological discoveries for the betterment
of human health if they receive the resources, time, and freedom to pursue challenging questions. The 298 investigators of HHMI, selected through rigorous
national competitions, include 12 Nobel Prize Winners and 122 members of the National Academy of Sciences. Founded in 1953 by Howard R. Hughes, the aviator
and industrialist, HHMI is headquartered in Chevy Chase, Maryland, and employs more than 2,600 individuals across the U.S

Results of world’s first gene therapy for inherited blindness show sight improvement!

2008-04-27T14:30:00.003+02:00

UCL PRESS RELEASE

UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital have announced results from the world’s first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness. The results, published today in the New England Journal of Medicine, show that the experimental treatment is safe and can improve sight. The findings are a landmark for gene therapy technology and could have a significant impact on future treatments for eye disease.

The trial, which received funding from the Department of Health, represented a world first when it began in February 2007. It involves young patients with a condition called Leber’s congenital amaurosis (LCA), a rare inherited eye disease caused by an abnormality in a gene called RPE65. The condition appears at birth or in the first few months of life and causes progressive deterioration and loss of vision. There are currently no effective treatments available. The trial’s purpose was firstly to find out whether gene therapy for retinal disease is safe, and secondly to find out if it can benefit vision in young adults who already have advanced retinal disease.

Crucially, the experimental treatment was found to cause no side effects in this trial. Following the treatment, the three patients involved underwent a series of tests designed to establish the effects of the therapy on vision. They all achieved levels of vision at least equivalent to before the operation, but one patient (Steven Howarth, 18) benefited from significantly improved night vision. This was demonstrated by his ability to negotiate a specially constructed simulation of a night-time street scene. Before the operation he completed the task slowly and made several mistakes, but following the surgery he was able to navigate quickly and without mistakes.

The researchers believe the operation’s success for this particular patient could be because his disease had not progressed to the same extent as the others. The other two patients may also still benefit from the new treatment in the future, but it will be some time before this becomes apparent. The team have already begun to trial the technique in younger patients, where they hope to achieve even better results.

The team conducting the trial, from the joint Moorfields Eye Hospital/UCL Institute of Ophthalmology NIHR Biomedical Research Centre, is led by Professor Robin Ali and includes eye surgeon Mr James Bainbridge and retinal specialist Professor Tony Moore. The technique used in the trial involved inserting healthy copies of the missing RPE65 gene into the cells of the retina to help them to function normally. This involved an operation which delivered the normal genes to the retina, using a harmless virus or ‘vector’ to carry the gene into the cells – the vector was manufactured by US company Targeted Genetics.

Commenting on the findings, Professor Ali said: “Showing for the first time that gene therapy can work in patients with eye disease is a very significant milestone. This trial establishes proof of principle of gene therapy for inherited retinal disease and paves the way for the development of gene therapy approaches for a broad range of eye disorders.”

Explaining the technique, Mr James Bainbridge, who leads the surgical team, said: "We developed surgical techniques to enable access to the cells beneath the retinas of patients, using a very fine needle to deliver the modified virus in a controlled retinal detachment that resolves as the vector is absorbed. It is tremendously exciting to see that this technique is safe in an extremely fragile tissue and can improve vision in a condition previously considered wholly untreatable."

Professor Moore said: “It is very encouraging to see that this treatment can work, even in young adults who have severely advanced disease. We anticipate an even better outcome in the younger patients we are now beginning to involve as the trial proceeds, as we will be treating the disease in the early stages of its development.”

Professor Ali added: “These results give us great confidence that this technique is safe and can bring real benefit to patients with impaired vision. While we’re very excited about the improvement in Steven’s vision, it’s important to emphasise that gene therapy is still an experimental treatment not yet generally available to patients. The technique will be tested in other patients with LCA and we also hope to begin trials for other forms of retinal disease in the future.”

About Moorfields Eye Hospital/UCL Institute of Ophthalmology NIHR Biomedical Research Centre

The Centre was established in April 2007, funded by the Department of Health through the National Institute for Health Research (NIHR). It is one of 12 NHS-university partnerships that have been awarded Biomedical Research Centre status, following an international peer reviewed competition based on an outstanding international reputation for medical research and expertise, and experience of translating that research into the clinical setting.

The results from this gene therapy trial are the first significant outcome from the establishment of the centre, and strongly demonstrate its purpose - to conduct translational research designed to take advances in basic medical research from the laboratory to the clinic, enabling patients to benefit more quickly from new scientific breakthroughs.

About UCL Institute of Ophthalmology

UCL Institute of Ophthalmology is one of a number of specialised research centres linked to UCL (University College London) and is, together with Moorfields Eye Hospital, one of the leading centres for eye research. The Institute scored 5*A (the highest possible rating) in the last Research Assessment Exercise and is committed to a multi-disciplinary research portfolio that furthers an understanding of the eye and visual system, linked with clinical investigations targeted to specific problems in the prevention and treatment of eye disease. The combination of the Institute’s research resource with the resources of Moorfields Eye Hospital, which has the largest ophthalmic patient population in the Western World, opens the way for advances at the forefront of vision research.

About Moorfields Eye Hospital NHS Foundation Trust

Founded in 1804 and opened in 1805, Moorfields Eye Hospital is one of the world’s leading centres for ophthalmic treatment, teaching, and research. It is the oldest and largest specialist eye hospital in the world, and became one of the UK’s first NHS Foundation Trusts in 2004. More than half the ophthalmologists practicing in the UK, and many more overseas, have received specialist training at Moorfields. As well as its main site based on City Road, EC2 the Trust has over 1,300 staff spread over ten sites in Greater London. They are able to treat the entire range of eye diseases
from cataracts, to more complex conditions, and patients come to them from all over the UK and the world.

Story taken from
http://www.ucl.ac.uk/ioo/research/patients/clinical_trials.html

LCA gene therapy trial: directly from the first participant

2008-01-16T18:30:00.000+01:00

After introducing himself on this blog a while ago (and what a big surprise that was!), Billy, the first LCA patient to take part in a gene therapy clinical trial, has joined the LCA mailing list and bravely faced the flood of questions that obviously came his way.

Amber, a member of the LCA list who runs a very interesting and informative site on LCA, has patiently put together Billy’s comments and replies, which are now available on her web site at
http://www.wonderbaby.org/articles/lca-gene-therapy-trials.html

Do read this incredible developing story, and stick around for more!

I personally thank Amber for her work, and once again I thank Billy for being willing to share his experience with all of us.

Fran

It's time for the next LCA conference!

2008-01-14T19:46:00.000+01:00

LCA Research is going strong, more genes are being discovered, animal experimentation is under way in so many labs, even human trials have begun! It’s really time for another LCA conference!

The Foundation for Retinal Research is partnering with Project 3000 for this year’s LCA Conference, a unique opportunity to learn first hand the most current information on LCA directly from the researchers and doctors who are working on it.

Medical exams, ERGs and retinal photographs will also be offered through the Cole Eye Institute at the Cleveland Clinic. These exams will be offered on Thursday, July 24 and Friday, July 25. The conference itself will be held on July 26th and July 27th at the InterContinental Hotel and Conference Center.

Please visit the FRR web site
http://www.tfrr.org
to receive more information, to register for the conference and to request medical exams. Please make your reservations quickly as space is limited.

Note: for hotel reservations call the hotel and ask for the LCA rate. Booking on the web site will not give you access to the discounted rates.

One more LCA trial for RPE65

2007-11-20T21:02:00.000+01:00

Great news!
Phase 1 gene therapy clinical trials for Leber's Congenital Amaurosis caused by RPE65 have begun at the University of Pennsylvania and the University of Florida! One volunteer patient has received an injection of genes into the retina of one eye. The injection was performed by Shalesh Kaushal, MD, PhD, assistant
professor of ophthalmology at the University of Florida. Six adults and three children between the ages of 8 and 17 years are scheduled to undergo the procedure at the university over the next year.

This is the second gene therapy trial for RPE65, commencing only a few months after the one currently underway at London’s Moorfields Hospital. It will take a while before results from both trials are disclosed, however if things go well the good news should start to leak out soon.

The Foundation for Retinal Research Newsletter, October 2007

2007-10-25T19:32:00.000+02:00

FRR VisionsThe newsletter for families and supporters of the Foundation for Retinal Research October 2007 www.TFRR.org • info@tffr.org • 1-224-927-5063 Sally Lewinski, editorFamily to FamilyA team of doctors at Children’s Hospital of Philadelphia (CHOP) has been given approval to carry out a clinical trial evaluating gene therapy for a form of Leber Congenital amaurosis (LCA) caused by mutations in the RPE65 gene (see attached brochure). This new experimental procedure has been rigorously tested in animals since the first injection performed in the famous dog, Lancelot, in July 2000 (Lancelot is still enjoying vision and occasionally leaves his children and grandchildren at the University of Pennsylvania to attend meetings and fundraisers.) The safety and efficacy data funded, by the NEI/NIH, Research to Prevent Blindness, and Foundation Fighting Blindness, have been published in peer-reviewed journals, and have been reviewed carefully by a large set of committees, including the CHOP Institutional Review Board (IRB) and the Food and Drug Administration (FDA). Studies in adults with this disease have initiated or soon will be initiated at other sites (Moorfields Eye Hospital and University of Florida, Gainesville). Because there may be a higher likelihood of restoration of vision in a pediatric population than in an adult population, the Principal Investigator of the CHOP trial, Dr. Albert Maguire, argued at the Recombinant DNA Advisory Committee (RAC) at the National Institutes of Health (NIH) in December 2005, that the risk/benefit ratio of a clinical trial in a pediatric population with this disease is acceptable. There are several gene therapy studies that have been or are in the process of being performed in adults with ocular diseases. The strategies include delivery of a compound thought to inhibit blood vessel growth in individuals with the “wet” form of macular degeneration, and delivery of encapsulated cells engineered to secrete a neurotrophic factor to individuals with retinitis pigmentosa. The only ocular gene therapy trial performed to date in pediatric subjects was one aiming at treating the deadly eye cancer called retinoblastoma. Gene delivery in that trial was deemed safe, and there was even some evidence of efficacy. The trial for LCA-RPE65 at CHOP is the first study involving older children (and young adults) with retinal degeneration. If the treatment is shown to be safe in this trial, younger subjects could be enrolled in future studies. This study could also pave the way for developing treatments not only for this form of LCA but for other genetic forms of LCA and other retinal degenerative diseases. Children’s Hospital of Philadelphia, which has been recognized by US News and World Report (and also Parents Magazine and Child Magazine) as the best Children’s Hospital in the USA for the past 5 years (http://www.chop.edu/consumer/news/story.jsp?id=86934), has been extremely supportive of the pediatric clinical trial for LCA-RPE65. A unique aspect of this study compared to studies that involve adult subjects, lies in the differences in evaluating and treating children versus adults. It is well recognized that developmentally, cognitively, anatomically, and medically, the pediatric patient is unique and fundamentally different from the adult. For example, most institutions do not have the experience that CHOP has in obtaining assent of a child (and permission of the parents) for participating in a clinical trial. Methodology and instrumentation that has been widely used in the assessment and treatment of adults have not been validated in children, and in many cases, are irrelevant. Dr. Eric Pierce, a Sub-Investigator in the LCA-RPE65 clinical trial at CHOP, has established the first Center for Pediatric Hereditary Retinal Degenerations in the USA. He and Dr. Maguire also work closely with other physicians at CHOP who have vast clinical trial experience for diseases such as Retinopathy of Prematurity and amblyopia. In addition, Dr. Maguire has clinical trial experience for a number of other pediatric and adult eye conditions, including studies involving age-related macular degeneration, retinal holes, uveitis, and the ocular complications of AIDS. CHOP has a tradition of investing heavily in the development of new treatments which can save lives and improve the quality of life for children. Among the historical research breakthroughs that have made CHOP an international pioneer in pediatric medicine are the use of gamma globulin for prevention of hepatitis A and B, discovery of the association between infectious mononucleosis and Epstein-Barr virus infection, vaccines against measles, mumps, rubella, whooping cough and influenza, the development of a balloon catheter for use in cardiology, the invention of the isolate incubator for newborns, the first in-depth understanding of “shaken baby syndrome,” and the generation of methods for changing sickle-shaped red blood cells. The legacy of pediatric breakthroughs continues today, exemplified by the recent development and approval of the rotavirus vaccine. Recently, CHOP established the Center for Cellular and Molecular Therapeutics (CCMT), Dr. Katherine High, Director. The CCMT is a team of highly regarded scientists and physicians engaged in development of genetic therapies. The CCMT has been working closely with the scientific director of the trial, Dr. Jean Bennett, a professor of ophthalmology at University of Pennsylvania’s Scheie Eye Institute, and Dr. Jeannette Bennicelli, a senior scientist in the Bennett laboratory, to plan this trial. The CCMT includes a Clinical Grade Vector Core, which develops the pharmaceutical grade reagents that are used in clinical trials. The Director of that facility, Dr. Fraser Wright, has extensive industry experience in generating reagents used for clinical studies in Parkinson’s disease and hemophilia. Further, Jennifer McDonnell, Dr. Valder Arruda, and other members of the Center have extensive experience with regulatory and administrative issues related to clinical gene transfer, and issues of special importance in the pediatric research population. Finally, the Center is very familiar with the practical issues that are faced in carrying out clinical trials, including logistics of travel and accommodation of children and their parents. For the LCA-RPE65 study, CCMT has engaged a first rate clinical coordinator, Kathleen Marshall, who has over 25 years experience in diagnosis and treatment of ophthalmic disorders in children. Finally, CCMT has assisted in developing an additional outcome center for this trial in Naples, Italy, so that participants from Europe can be evaluated after injection closer to home. Clinical outcome centers in additional countries, including Brazil, are in the process of being established. The LCA-RPE65 clinical trial has also received substantial support from University of Pennsylvania’s Scheie Eye Institute and the Department of Ophthalmology and the F.M. Kirby Foundation. Several of the physicians and scientists, including Drs. Maguire, Pierce, and Bennett, have primary appointments in this Institute and their laboratories are in the F.M. Kirby Center for Molecular Ophthalmology at University of Pennsylvania.Dr. MaguireChildren’s Hospital of Philadelphia enrolling LCA patients for clinical trialsBy Atom and Sonja Biggs"Your boy weighs 7 lbs., 15 oz. He would have been 8 lbs. if he hadn't peed on the way out," said the nurse jokingly. In every way our firstborn son seemed perfectly healthy and happy as he ate and grew and learned how to crawl like any other baby. At age one Brandon learned how to walk. As he became more adept at locomotion he also encountered more frequent collisions, most often with tall, slender objects like table legs, or toys and furniture that had been moved from their usual spots. We also observed strange behavior at the dinner table. When food was placed in front of Brandon, instead of looking for it he would stare off into the distance, patting around with his hand until he found his food. Was he absorbed in thought? Clumsy? Or was there something wrong with his vision?We first brought Brandon to an optometrist who assured us that many young toddlers are bit farsighted and that as first-time parents we might be a bit oversensitive. The next 3 months were fraught with more and more accidents. Finally, after a couple of bloody collisions at Sonja's mother's home, we took him to see a pediatric ophthalmologist. Tests showed extensive retinal degeneration. "Your son is mostly blind in both eyes," we were informed, "and may lose all of his sight as he gets older."(Continued on page 5)In spite of his parents' worries and concerns, Brandon insisted upon growing up like any other little boy. He was throwing snowballs, hiking trails, and assembling his new baby brother's crib. When we informed Brandon that he would never be able to drive a car, he developed a determination to somehow obtain a car. At age 5 Brandon started raising baby hamsters and selling them to the pet store. With the money he raised from hamster sales and from watching over his new baby brother Brandon bought himself a kidsize electric jeep. He spent hours puttering around our spacious back yard, his little brother belted into the passenger seat.At age 6 dad tried unsuccessfully to teach Brandon how to stay up on a bicycle. But Brandon wasn't ready to give up. All winter long Brandon practiced in the basement of his house, and that spring he emerged outside riding like a champ!Brandon continued to grow up with a spirit of determination and tenacity. Joining 4H, he showed first hamsters, then chickens, lambs, and rabbits. Loving to receive awards Brandon quickly plastered his walls with ribbons, plaques, and trophies. He was competitive in track & field and cross country running. But when Brandon said he wanted to try out for 7th grade basketball Dad drew the line, because he could see neither the ball nor the basket. But Brandon was determined. He arranged a meeting of his parents, teacher, the principal, and coach, and pled his case for equality. He won. Brandon was the team's top guard and played every game.Brandon's voice had always been clear and distinct, frequently loud. Not surprisingly, he joined the regional speech contest and won. Then he performed in a school musical and enjoyed himself immensely. So he put all of his savings toward performing arts camp for the next summer, auditioned, and was in. That was just the beginning of his drama fever. Since then Brandon has performed in six musical productions including Oliver, Cinderella, and now Beauty and the Beast. His dream is to make acting his career.Brandon's path has rarely been a smooth one. From his numerous scrapes and scars he can outline his life's story. And perhaps the most difficult obstacle Brandon has had to face has not been his poor eyesight. It has been the limits placed on him by those of us who have sight. But Brandon meets all prejudice and obstacles head on with humor, a positive spirit, and a strong faith believing that God is with him. When one door is locked tight he finds another door that will open. Brandon continues to be a real inspiration to all of us.Brandon BiggsThis newsletter is sponsored by the SPECIAL KIDS NETWORKwww.SpecialKidsNetwork.orgBy Amber BobnarAs the holidays approach, some of us just dread the thought of writing out that long shopping list and racking up painful charges on our credit cards. But what if you could finish your holiday shopping weeks in advance, give meaningful gifts to all your loved ones, and help FRR make a difference all at the same time?In place of scented candles or 2008 calendars, consider giving tribute gifts to all your friends and family this year. Tribute giving, sometimes referred to as honor giving, is the donation of money to a charity in someone else's name. Instead of fighting your way through the malls this December, simply donate your holiday budget to FRR and do away with all the stress – and January returns, too!And what about what everyone is getting you this year? Why not turn this season into a sort of FRR Holiday Campaign? Get all of your friends and family in on the event by pledging to both give and receive as many tribute gifts to FRR as possible this year. You could even begin an annual tradition of giving and try to top your total donation amount each year.If organizing an entire holiday event sounds too daunting, you could always just throw a simple holiday party and ask that each guest donate a bit of holiday cheer to an FRR Holiday Donation Bowl set in the middle of the hors doeuvre table. This way there's less pressure to give, but you can still end up making a difference by the end of the evening.But you don't have to stop there. There are many ways to bring people together to help FRR, especially over the holiday season. Can you get your child's school to organize a giving event? Or maybe your local church? Remember, 'tis the season to spend time with your loved ones, help others in need, and give when you can. And if tribute giving can also help relieve your holiday stress, all the merrier! For more information about tribute giving or organizing a fundraising event, visit the FRR website at www.tfrr.org.This newsletter is sponsored by the SPECIAL KIDS NETWORKwww.SpecialKidsNetwork.orgSupport FRR this holiday seasonPROJECT 3000 and You!
By Heather Scherber, Project 3000Just over one year ago, Chicago Cubs’ Derrek Lee, received the news that many of you are all too familiar with: their child was visually impaired due to LCA.They met with Dr. Edwin Stone, director of the University of Iowa’s Carver Family Center for Macular Degeneration, partnered with Wyc Grousbeck (owner of the Boston Celtics, whose son has LCA) and formed Project 3000. Since that time, Project 3000 has been blessed with the support of the Cubs organization, the Foundation for Retinal Research, generous individuals, and numerous families affected by LCA.Today we are proud to say that together we ARE making a difference! The following are highlights from the past year. We’re Being Heard! There has been a tremendous increase in awareness of LCA. The combination of press conferences, news reports, pre-game and intra-game interviews, and numerous Project 3000 Days at Wrigley Field and many minor league baseball parks have reached millions of people with this message: “There is something you can do”. Website hits, emails and phone inquiries about genetic testing for LCA have increased ten-fold since Project 3000 began.Medical Support is Growing! The directors of every ophthalmology training program in the U.S. have been contacted and informed about Project 3000. Dr. Stone will present a talk about LCA to the opening session of the annual meeting of the American Academy of Ophthalmology in New Orleans this November.Testing is Faster! The molecular methods that underlie the genetic test for LCA have been extensively refined and improved so that the chance of finding the specific molecular cause for an individual patient with LCA is now nearly 70% (up from about 50% one year ago). Even though additional genes have been added to the assay, the full test can now be performed 43% faster than it could one year ago.We Can Test Every Sample! The infrastructure of the Carver Laboratory has been dramatically increased so that samples from all remaining LCA patients in the U.S. could be received in a single year if these individuals could be identified and were willing to submit samples.Funding is at an All Time High! More than $1M in philanthropic support for Project 3000 has been raised in the past year. A “no overhead” mechanism has been devised for handling these gifts through the University of Iowa Foundation. As a result, these funds are sufficient to provide state-of-the-art genetic testing for over 1000 families who lack insurance coverage or personal resources to pay for the testing themselves.More Samples are Coming in Than Ever Before! More than one sixth of the LCA patients in the US have already been tested for mutations in the known genes, and the results of this testing have been summarized and accepted for publication in a scientific journal. New samples from LCA patients are being received by the Carver Labs at 5 times the rate they were before Project 3000 began and in the past 12 months, LCA samples have been received from 22 different states.We’re Moving Forward! A large volunteer infrastructure has been built for contacting LCA patients on a state-by-state basis. In the first year, specific emphasis has been placed on developing this infrastructure in Iowa, Illinois, Massachusetts, California, New York, Florida, Texas, and Kentucky. These eight states represent more than 40% of the population in the U.S. In many states, the Lions Clubs have been engaged as partners. A full-time external relations director has been hired to oversee these efforts from Iowa City. We’re Getting the Word Out to 11 Million People!! On January 17 the hit show “ER” will feature an LCA awareness episode! Although the story line has not been completely developed, it will feature a child being tested and diagnosed with LCA. To close the episode, there will be an informational piece on Project 3000. *Air Date is Subject to ChangeIf you would like more information on Project 3000 or, to join our mailing list, please contact us in one of the following ways:Visit: www.project3000.org orwww.1sttouch.orgWrite: 1st Touch Foundation5921 Maleville AveCarmichael CA 95608Call: Heather Scherber, Development Associate(916) 212 -0312
SAVE THE DATE! Next FRR Family Conference will be in August 2008 in Cleveland!More information will follow. Please check www.TFRR.org!Ivan BobnarFrom: Walla Walla Union-Bulletin, WA, July 15, 2007By: Andy PorterofDIXIE - Brandon Biggs may be nearly blind, but that doesn't stop him from seeing himself as an actor.Among the cast for the summer musical ``Cinderella,'' Biggs sings and dances his way through several roles in the play. Although the audience can see him, only a few on the other side of the footlights may know he can't see them.Visually impaired since birth, the curly-haired 15-year-old has refused to consider his blindness a handicap, said his parents, Atom and Sonja Biggs.It hasn't dented his sense of humor either.``We do everything we can as parents to support him,'' Sonja said last week at the family's home in Dixie.``Except for driving,'' Brandon quipped from where he was sitting on a couch.``And when he wanted to make his own fireworks, we wouldn't let him,'' his mom added.Medically speaking, Brandon's condition is diagnosed as Lieber's congenital amaurosis. He can discern vague shapes and color, but not detail, although his peripheral vision is more acute than his frontal sight.But the condition has not stopped his son from pursuing interests that have run from raising lambs to earn tuition for acting camp to competing in multiple sports, Atom said.``He runs three miles a day and then does weight training,'' his father noted. Brandon also does his share of chores on the family's country home alongside his younger brother, Joshua.According to Atom and Sonja, the acting bug bit Brandon early.``Growing up, he's always been the one to be the storyteller,'' Sonja said.The urge to act led to roles in school plays in Dixie and Waitsburg and then, last August, a summer course with the Missoula Children's Theater performing arts camp in Missoula, Mont., followed by a role at Dayton Liberty Theater in the production of``Oliver.''Brandon will return to acting camp again this year and then will begin rehearsals for the part of the prince in Touchet Valley Arts Council's production of ``Beauty and the Beast.''In ``Cinderella,'' Brandon has to stay on his toes, given that his roles are listed as ``footman/ball attendant/assistant steward/guard.''Among challenges he has faced have been memorizing how and when to react to gestures by his fellow cast members to learning where props are placed so he doesn't collide with them.``Cinderella'' director Paul Wickline said that in working with Brandon, the safety issue was a concern ``but everything else was up to him.''``It's dangerous out there (on the stage).'' Wickline said. ``There's all kinds of sharp corners and potholes. So what we tried to do was have him in things we knew he could do successfully and safely'' during action on the stage.Wickline said another aid has been to have Brandon paired with other actors during scenes so he can physically relate to his surroundings and act accordingly.While the on-stage action is one thing, Brandon said, his fellow cast members ``all worry about when I'm walking around backstage,'' concerned that he may trip and fall over a wayward prop.``You should be carrying your cane when you're back there,'' Sonja said.``I've got a spear. It works the same,'' Brandon said with a smile.Brandon Biggs takes on several roles in the summer musical, `Cinderella’A Cinderella StorySummer musical ``Cinderella'' actor Brandon Keith Biggs, a sophomore this fall at Walla Walla High School, has several other roles under his belt and a strong interest in pursuing a career in theater. He is also nearly blind.our vision is clear(continued from page 1)In spite of his parents' worries and concerns, Brandon insisted upon growing up like any other little boy. He was throwing snowballs, hiking trails, and assembling his new baby brother's crib. When we informed Brandon that he would never be able to drive a car, he developed a determination to somehow obtain a car. At age 5 Brandon started raising baby hamsters and selling them to the pet store. With the money he raised from hamster sales and from watching over his new baby brother Brandon bought himself a kidsize electric jeep. He spent hours puttering around our spacious back yard, his little brother belted into the passenger seat.Atom tried unsuccessfully to teach Brandon, at age 6 how to stay up on a bicycle. But Brandon wasn't ready to give up. All winter long Brandon practiced in the basement of our house, and that spring he emerged outside riding like a champ! Brandon continued to grow up with a spirit of determination and tenacity. Joining 4H, he first showed hamsters, then chickens, lambs, and rabbits. Loving to receive awards Brandon quickly plastered his walls with ribbons, plaques, and trophies. He was competitive in track & field and cross country running. But when Brandon said he wanted to try out for 7th grade basketball Dad drew the line, because he could see neither the ball nor the basket. But Brandon was determined. He arranged a meeting of his parents, teacher, the principal, and coach, and pled his case for equality. He won. Brandon was the team's top guard and played every game.Brandon's voice had always been clear and distinct. Not surprisingly, he joined the regional speech contest and won. Then he performed in a school musical and enjoyed himself immensely. So after putting all his savings toward performing arts camp for the next summer, he auditioned, and was in. That was just the beginning of his drama fever. Since then Brandon has performed in six musical productions including Oliver, Cinderella, and now Beauty and the Beast. His dream is to make acting his career.Brandon's path has rarely been a smooth one. From his numerous scrapes and scars he can outline his life's story. And perhaps the most difficult obstacle Brandon has faced has not been his poor eyesight, but the limits placed on him by those of us who have sight. Brandon meets all prejudice and obstacles head on with humor, positive spirit, and believing that God is with him. When one door is locked tight he finds another door that will open. Brandon continues to be a real inspiration to all of us.the pediatric patient is unique and fundamentally different from the adult. For example, most institutions do not have the experience that CHOP has in obtaining assent of a child (and permission of the parents) for participating in a clinical trial. Methodology and instrumentation that has been widely used in the assessment and treatment of adults have not been validated in children, and in many cases, are irrelevant. Dr. Eric Pierce, a Sub-Investigator in the LCA-RPE65 clinical trial at CHOP, has established one of the first Center for Pediatric Hereditary Retinal Degenerations in the USA. He and Dr. Maguire also work closely with other physicians at CHOP who have vast clinical trial experience for diseases such as Retinopathy of Prematurity and amblyopia. In addition, Dr. Maguire has clinical trial experience for a number of other pediatric and adult eye conditions, including studies involving age-related macular degeneration, retinal holes, uveitis, and the ocular complications of AIDS. CHOP has a tradition of investing heavily in the development of new treatments which can save lives and improve the quality of life for children. Among the historical research breakthroughs that have made CHOP an international pioneer in pediatric medicine are the use of gamma globulin for prevention of hepatitis A and B, discovery of the association between infectious mononucleosis and Epstein-Barr virus infection, vaccines against measles, mumps, rubella, whooping cough and influenza, the development of a balloon catheter for use in cardiology, the invention of the isolate incubator for newborns, the first in-depth understanding of “shaken baby syndrome,” and the generation of methods for changing sickle-shaped red blood cells. The legacy of pediatric breakthroughs continues today, exemplified by the recent development and approval of the rotavirus vaccine. Recently, CHOP established the Center for Cellular and Molecular Therapeutics (CCMT), Dr. Katherine High, Director. The CCMT is a team of highly regarded scientists and physicians engaged in development of genetic therapies. The CCMT has been working closely with the scientific director of the trial, Dr. Jean Bennett, a professor of ophthalmology at University of Pennsylvania’s Scheie Eye Institute, and Dr. Jeannette Bennicelli, a senior scientist in the Bennett laboratory, to plan this trial. The CCMT includes a Clinical Grade Vector Core, which develops the pharmaceutical grade reagents that are used in clinical trials. The Director of that facility, Dr. Fraser Wright, has extensive industry experience in generating reagents used for clinical studies in Parkinson’s disease and hemophilia. Further, Jennifer McDonnell, Dr. Valder Arruda, and other members of the Center have extensive experience with regulatory and administrative issues related to clinical gene transfer, and issues of special importance in the pediatric research population. Finally, the Center is very familiar with the practical issues that are faced in carrying out clinical trials, including logistics of travel and accommodation of children and their parents. For the LCA-RPE65 study, CCMT has engaged a first rate clinical coordinator, Kathleen Marshall, who has over 25 years experience in diagnosis and treatment of ophthalmic disorders in children. Finally, CCMT has assisted in developing an additional outcome center for this trial in Naples, Italy, so that participants from Europe can be evaluated after injection closer to home. Clinical outcome centers in additional countries, including Brazil, are in the process of being established. The LCA-RPE65 clinical trial has also received substantial support from University of Pennsylvania’s Scheie Eye Institute and the Department of Ophthalmology and the F.M. Kirby Foundation. Several of the physicians and scientists, including Drs. Maguire, Pierce, and Bennett, have primary appointments in this Institute and their laboratories are in the F.M. Kirby Center for Molecular Ophthalmology at University of Pennsylvania.Children’s Hospital of Philadelphia enrolling LCA patients for clinical trialsBy Amber BobnarWe attended the Hawaii Association for Parents of the Visually Impaired's annual conference in 2006. HAPVI (along with the Hawaii Association for the Blind – HAB) had invited many state and federal representatives to attend the conference and explain to the members why so little was being done to help the blind, especially blind children, in Hawaii. Public transportation was a joke, the public schools were under funded and under staffed, and there was not a single TVI employed in the entire state to work with blind children aged zero to three. And nothing was being done to hire one!What was the response? Beside much evading, hollow promises, and empty apologies, we heard one phrase repeated over and over: "Blindness is a low incident disability."It may be a poor excuse, but nonetheless it is true that blindness is a low incident disability. 3% of the U.S. population is blind or visually impaired and only .4% of the general population is considered legally blind. If you look at the number of blind children in the U.S. (only .01% of the general population), you can begin to understand why many government officials just can't seem to find the time to staff or fund programs for visually impaired children.So what did we do? We tried our best to fight the system (and I like to think we made a few waves), then we moved.We now live in Watertown Massachusetts and the difference couldn't be greater. Watertown is home to the oldest School for the Blind in the country, Perkins. The great thing about living so close to Perkins is that the town is very accessible and blindness isn't a "low incident" anymore.Why is this important to us? On the surface, it means that signs around the school announce to motorists to slow down and be aware of white canes. It means that crosswalks talk to you (they say "please wait" after you press the button) and so do busses (by announcing every stop on a clear overhead speaker).But much, much deeper is the attitude of the community. Our son, Ivan, is no longer the only baby who is blind in town; in fact, white canes and seeing eye dogs are pretty common. People here aren't afraid of blindness like they often where in Hawaii. Most telling is the response we receive from people who have just learned that Ivan is blind. In Hawaii the attitude was dire, like we were suddenly at a funeral: "Oh, no. I'm so sorry. That's terrible." This always upset me because I knew that, even as an infant, Ivan was forming his identity and would begin to associate his blindness (and maybe even himself) with this grim reaction.But in Watertown it's been the exact opposite. When we meet someone new and mention Ivan's blindness, they light up: "Oh! Is he going to Perkins? That's wonderful! It's such a great school!" The people in Watertown are so proud of Perkins and it shows in their attitude. They smile, touch Ivan's hand, and begin the conversation on such a positive note. I know that this is just our experience, but living in such an open and understanding community has really helped us a lot. Moving so far away from home was a big decision (and don't worry, we do have lots of family in New England, too), but we wanted to do what was right for Ivan. I really believe community support will mean a world of difference for Ivan as he matures here at Perkins.(Oh, and the school really is great, too!)Moving to Perkins:
Why Community Support Means So Much To The BobnarsNote: Brooke Pernice is the daughter of PGA Tour golfer Tom Pernice Jr., and also has LCA. She recently put out her own CD of music. It is available at her website, www.BrookePernice.comI am Brooke Pernice, I am 12 years old and here's my story. I have always had a personal relationship with our Lord and Savior Jesus Christ. When I was seven years old, the good Lord spoke to me and said I would lead a worldwide ministry through music. I took this message seriously and started taking vocal lessons to work towards my future. Last September, the Lord sent some lyrics to my mother. My vocal coach and I reworked the lyrics slightly and the song "Standing on My Own " came to life. This song is a tribute to my sister Kristen. As the lyrics kept coming our way, my life was put to a song. I am blind and do see the world differently, as I like to say through song, I see the world, "From the Inside." The Lord spoke to me again in the fall and told me it was time to start doing concerts and public speaking. My debut CD tells my life through song. God Bless you all. Brooke PerniceBrooke Pernice releases music CD about LCA, blindnessAmber & Ivan Bobnar‘Special Kids Network’ golf outing raises $160,000 for childrenThe Special Kids Network, held its Annual Tennis and Golf event, August 6, 2007, at Twin Orchard Country Club in Long Grove. The 225 golfers, were not deterred by inclement course conditions from having an outstanding day. The golf outing was sponsored by Highland Park’s, Morris Silverman and Family, who also hosted the event at Twin Orchard. The evening before the event, Gibsons Restaurant at their Luxbar location hosted a dinner for Special Kids Network celebrity guests and sponsors. Joe Giardi, former Chicago Cub and 2006 Major League Baseball Manager of the Year, acted as the Golf-Outing Honorary Chairperson. The Women’s Tennis event was held in cooperation with the Midtown Athletic Club. The 35 women were treated to a fun-filled day with prizes handed out from Honorary Chairperson, Kathy Hart; from the Eric & Kathy Show - The Mix 101.9 FM. Billy Jaffe (Highland Park Native) and current Color Analyst for the New York Islanders on Fox Sports Network, New York acted as the Master of Ceremony. Among the other sports and media celebrities who played with various foursomes were, Trent Yawney, former Head Coach of the Chicago Black Hawks; Mark Giangreco of Channel 7 Sports; Eric Soderholm, former Chicago White Sox player; Jeremy Roenick, of the San Jose Sharks; Paul Popovich, former Chicago Cub player; Bob Murray, Senior Vice President of Hockey Operations for the Stanley Cup Champion Anaheim Ducks; Joe Corvo (Oak Park Native), and player for the 2007 Eastern Conference Champions, Ottawa Senators, and Emery Moorehead, from the Chicago Bears Super Bowl team. The event raised approximately $160,000.00, for the recreational programs of Keshet, which serves children and young adults with physical and developmental disabilities, as well as the Pediatric-Gastrointestinal Research Foundation at the University of Chicago Hospital, National Stuttering Association, Foundation For Retinal Research, and Glenkirk.The event was co-chaired by Garry Benjoya of Buffalo Grove; Trevor Brody of Chicago; Bonnie Brickman, Chad and Debbie Coe, and Scott Rudin of Deerfield; Steve Hara and Greg Solk of Highland Park; and Michael Rosen of Northbrook, and Steve Strumpf of Weston, Florida. The days festivities included, lunch and dinner, and a silent and live auction. Top premium items included, a trip to the Lexis Tournament of Champions at the Pebble Beach Golf Club. The Great Escape donated a spa, and a white gold diamond bracelet was donated by Shelle Jewelers of Northbrook. Guests also received a party favor from local Bannockburn Company, “Zizzle,” called “Lucky,” the Incredible Wonder Pup.Frank and Alisha Lieberman of Deerfield, and Bari and Marc Levin of Buffalo Grove, were inducted into the Special Kids Network Hall of Heroes for their commitment, hard work, and generosity to children’s charities. Next year’s event will be held Monday, August 4, 2008, at Twin Orchard Country Club in Long Grove. For information, visit www.specialkidsnetwork.org.The Special Kids Network is an official sponsor of the FRR newsletter. Visit their website at www.SpecialKidsNetwork.orgThe Foundation for Retinal Research sends out a big Thank You to all the families and organizations that have participated in recent events and making them so successful. Here is a list of 2007 fundraisers for the Foundation and the most recent accomplishments of the events. If you are interested in holding an event please look online at www.tfrr.org under fundraising events or contact me directly at amber@tfrr.org or 630-978-0547.Can you believe everything that is going on in our world these days? USA Today does a feature on Derrek Lee and LCA. There are three gene therapy trials proceeding that are getting the attention of Time and Newsweek. The television show ER will feature a character with LCA in a January episode. Over twenty families are doing events to raise money and awareness for LCA. The FRR Associate Board has formed and is meeting regularly to foster grass roots activities and that has all happened within the last six months. Imagine what tomorrow will bring. The message this quarter is simple. Everything all of us are doing is making a difference. We all live with the delicate balance of living in the present and imagining the future. It is hard for me to tell how you are dealing in the present but if it is anything like what is being done by all of you for the future you all better get some sunglasses because the future looks bright.   David BrintBetsy & David Brint Ronnie & Alan Schwartz
Aaron Brint Steven Brint, M.D. Claire & Richard Cortesi Sue & Paul Fishbein Arlene & Mark Frommer Sally & Tim Higginson Laurie Hochberg, M.D. Carolyn & Roger Horchow Audrey & Fred Horne Joyce & Dr. Sam KrainPam & Andy McGaan Andrew Schwartz Claudia & Steven Schwartz Susie & David Sherman Heidi & Gary Tyson Gerald J.Chader, Ph.D Irene Maumenee, M.D. Steven U.Brint, M.D. Constance Cepko, Ph.D. Eugene de Juan, M.D. Mark Humayun, M.D. Weng Tao, M.D., Ph.D. Josseline Kaplan, M.D. Stephan Daiger, Ph.D. Jean Bennett, M.D. Edwin Stone, M.D. Ph.D. FRR Board of DirectorsFRR Scientific Advisory BoardThank You to all families raising money for FRR!Dave BushlandChrissy & Mike CornellKaren IrvineLaura & Mark JohansenRachel MillerKimberly MoncmanKelly PlatteChris RockeyLee St. ArnaudFRR Associate Board our vision is clearPICTURESFREE MATTER FOR THE BLIND
The Foundation for Retinal Research666 Dundee Road, Suite 1104Northbrook, IL 60062This newsletter is sponsored by the SPECIAL KIDS NETWORKEli BomersGraham WalkerIsabelle NuttMary Rose BushlandWilliam RankineMelody & Elizabeth KorenGot a photo of your little champ or princess?Email Sally@TFRR.org and we’ll run it in a future issue!The Mission of the Foundation for Retinal Research is finding treatments and cures for Retinal Degenerative Diseases and supporting affected families.

ER will raise awareness on LCA

2007-09-25T22:00:00.000+02:00

Maybe I’m a little late with this, I’m sorry it has taken me a while, but the news is nonetheless terrific and needs to be posted.
On January 17th 2008, the TV series “ER” will air an episode featuring the story of a little child with Leber’s Congenital Amaurosis! The goal is to raise LCA awareness. We need to thank Chicago Cubs’ Derrek Lee for this. In return for this incredible opportunity, he’s making a cameo appearance in another ER episode which will air on October 18th.
“ER” writers have had extensive conversations with LCA researchers, as well as Derrek’ lee and the people at his 1st Touch Foundation, asking for insight and suggestions. This is wonderful and will ensure that we make the most out of this unexpected, powerful opportunity.

The air date and the story are subject to change; I'll post more if I learn anything useful.

Fran

Big step forward in gene therapy technique for photoreceptors

2007-08-24T15:48:00.000+02:00

We all know of the huge success obtained with gene therapy for RPE65 Leber’s Congenital Amaurosis, at least in dogs, which is paving the way for similar experiments with different LCA genes. There is however an important difference between RPE65 and most other genes that cause LCA. While the former is expressed in the retinal epithelium (RP), other LCA genes are expressed primarily in photoreceptors. Since photoreceptors are much more difficult to access than the RP, the methods used for the RPE65 trials may not work for photoreceptor-specific gene replacement. But this obstacle is being overcome.
Researchers led by Dr. Alberto Auricchio, of the Telethon Institute for Genetics and Medicine (TIGEM), based in Naples, Italy, has identified viral vectors that can access rods and cones of mice more efficiently than those previously studied. These are extremely encouraging and important findings. Hopefully these techniques will work just as well on humans!

The paper has just been published in the August issue of the Journal of Virology. It is highly technical, but obviously worth reading.

I feel like an astronaut

2007-07-06T19:34:00.000+02:00

These days I really feel like someone who might become an astronaut, at least, someone who is working hard toward that goal. OK I know I was intending this blog to be strictly scientific, but given the recent medical advances, can you allow a personal touch?

One of my childhood dream was to become an astronaut. Unlike many childhood dreams, this stuck with me. Of course I always knew that I would not become one when I grew up.
I always considered my blindness to be the real big obstacle in my way. I know, we tend to focus our attention on those things that make us feel weakest...In blaming my lack of sight so much I was overlooking, for instance, that in order to be an astronaut you usually need to be a scientist of some sort, and...I can hardly go beyond algebra without my brain going on fire! I was also overlooking the fact that astronauts have to be in perfect shape; though I am very fit, well I admit it, I can get kind of sick when I go on my swing sometimes...LOL. And last but not least, well, not all scientifically-oriented, highly motivated, healthy athletes end up in space!
Anyway, apart from these wise considerations, my blindness still did have a role in spoiling some of my life’s plans, and not just the “plan” of going on a space ship.
Now though, blindness may be bringing something exciting my way, and I’m realizing it only now that retinal research has reached the human trial stage.

What if it really happens? What if a trial for my type of LCA gets planned, approved and patients are recruited. And what if I make a good candidate for such a trial?? It now seems feasible. What will happen next?

Learning how to see, no matter how little I will be able to see, will be like embarking on a thrilling, defying exploration of a new, unknown place. I’ve never seen anything beyond light and shadows. Even if I only get to see some shapes, how will it feel? Will there be sensory overload for a while? How long will it take before I begin to figure out what my eyes are sending to my brain? How will it feel?? The fact is, nobody can answer these questions right now, because it has never been done before.

Learning how to see. Stepping out into the unknown. Experiencing new sensations. Taking a daring step toward something of which nobody knows the outcome. Doesn’t it all sound a bit like what the astronauts do?

Astronauts get to experience 0G. They get to experience incredible accelerations, then float in their space ship where up and down loses most of its meaning, as they watch the earth spin below them, in a sky full of stars. All brand new, unimaginable sensation. Well, won’t seeing a shape feel almost as strange and thrilling to me as riding a space ship might feel to them?
Astronauts bring crucial knowledge to mankind. I won’t go so far to claim that my newly acquired sight will be half as useful to the world, however it certainly will be very interesting to researchers, physicians, and psychologists (hopefully not psychiatrists!) to witness how someone blind from birth can adjust to the new sensory input.
Astronauts must have a powerful spirit of adventure. Space is the new frontier, Their adventure is exciting, fulfilling, scary. If I’m given the chance, I too will undertake a big adventure. Like all adventures, it may be dangerous, but I’m eager to take the risk. If the heroes in the Challenger and Columbia missions were prepared to sacrifice their lives, I must be at least prepared to face unplanned consequences for my health or whatever happens. Like all adventures it may fail...I must be prepared for it. Many great candidate astronauts never actually made it to lift off.

I’ve always felt I was born for great things. But as I realized that I had no special talents and was just an ordinary girl, I simply began to ignore that thought. Now there may be a defying enterprise planned for me after all. And my blindness, which I always saw as my bitter enemy, may be the one thing that will allow me to come closer to space flight...

OK I know, it’s not the same! Being an astronaut is much better than being an eye patient... OK, I would still so much prefer to be born sighted and spare myself all the trouble. But unless I was born with a more developed scientific brain :-) along with good sight, I still would not become an astronaut...Therefore, as is wise, I try to ignore the bad and only keep the good.

Hopefully I’ll be “in space” in a couple of years....! And then, at least, I might be able to watch the stars. Being an astronomer is another of my childhood dreams that stuck, but....OK, now back to strictly scientific matters...

Thanks for reading me blabber.

Fran – Italy, 36, LCA CEP290 gene

The Foundation for Retinal Research Newsletter, June 2007

2007-06-28T19:30:00.000+02:00

FAMILY TO FAMILY
May 5 was a dream come true.
When we walked into Wrigley Field that day and saw people wearing the “Play for LCA” shirts, I began to cry. For 10 years now, we’ve been trying to make people aware of, and educate people about, LCA.
On May 5, for the first time, acceptance and awareness were everywhere. LCA moved up to the ‘majors’ in terms of being talked about. It is not just an issue now for the few - it is an issue in the hearts of everyone who loves the Cubs and Derrek Lee, whose daughter has LCA.
Project 3000’s mission is not only doable, but it is happening. The timing is perfect. Human trials for gene therapy are beginning and making international news. All the efforts of The Carver Lab, First Touch, FFB and FRR are making a difference.
Dr. Ed Stone did a wonderful job on both TV and Radio. They were smart enough not to allow us to talk (I think I would have cried my eyes out).
Alan got to sit in the radio booth and he was in heaven! Alan has fallen in love with baseball this year - he listens to every game on the radio - so to be there as the announcers were talking was surreal for him. They were all so nice to him and spent time talking to him during commercials.
We are grateful that we were able to participate. I only wish all the FRR families could have been there. Not only did the Cubs win - but we all did!
To read more about ‘Play For LCA” day at Wrigley Field, please turn to pages 4-5.

Drs. start LCA gene therapy
LONDON (Reuters) - A team of British doctors in May carried out the world’s first eye operations using gene therapy to try to cure a serious sight disorder.
The group from Moorfields Eye Hospital and University College London (UCL) has operated on a small number of young adults with Leber’s congenital amaurosis, a type of inherited childhood blindness caused by a single abnormal gene.
The condition prevents the retina from detecting light properly, resulting in progressive deterioration and severely impaired eyesight. There is no effective treatment.
The new experimental procedure involves inserting normal copies of the faulty RPE65 gene into cells of the retina -- the light-sensitive layer of cells at the back of the eye -- using a harmless virus or vector.
The British doctors are working alongside Seattle, Washington-based biotech firm Targeted Genetics Corp., which made the vector being used in the Phase I/II trial.
It will be several months before the success of the procedure can be properly assessed but medics said there had been no complications so far.
The move into human testing follows 15 years of laboratory and animal experimentation, including tests on dogs whose vision was restored to the extent they could navigate a maze with ease.
“Testing it for the first time in patients is very important and exciting and represents a huge step towards establishing gene therapy for the treatment of many different eye conditions,” Robin Ali, professor of human molecular genetics at UCL, said in a statement.
The clinical trial was given 1 million pounds ($2 million) of funding by Britain’s Department of Health, which said the pioneering research underlined the country’s leading position in gene therapy in Europe.
The idea of using gene therapy to fix diseases caused by genetic faults has long appealed to scientists, although getting the idea to work in practice has proved tricky.
Some gene therapy approaches have helped patients. But one 18-year-old volunteer died in a gene therapy experiment in 1999 and two French boys cured of a rare immune disease later developed leukemia.
Over 70 percent of gene therapy trials to date have been for cancer, where the process is complicated by the need to reach multiple sites in the body.
The eye, by contrast, is relatively straightforward, said Andrew George of London’s Imperial College.
“The eye is good for gene therapy because it is a simple organ and it is easy to see what is going on. There is hope that once gene therapy is developed in the eye, scientists could move on to more complex organs,” he said.

Here comes trouble - Hurray!
Last week, my charming and perfect son got suspended from school. Yep – you read it right – David and I found ourselves sitting in the principal’s office with Alan, his fourth grade teacher, his Braille teacher and the school social worker. It seems that our adorable little child has been experimenting with naughty words. Now Alan is smart enough to know that he can’t get away with using bad language at home or at school, but, he is a ten year old boy who is intrigued by swear words (yes, he has an older sister and brother) and the thought of four-letter words makes him giggle.
Alan used unacceptable language in a way that he thought no one would ever find out, and let me tell you, it was pretty clever. Alan uses a Braille Note at school to do most of his homework assignments. Other than Alan’s Braille teacher, Alan is the only one who really knows how to use it. Knowing that his Braille teacher never looked through Alan’s files in the Braille Note, Alan began to name all of his homework files very naughty names. He figured no one would know because when he prints out his homework, the file name does not show up. Unfortunately for my little juvenile delinquent, his Braille teacher happened to find the files while looking for something else. Oops.
This little stunt resulted in a one-day suspension from school and the loss of unsupervised use of his Braille Note for the rest of the year. Guess what? I am thrilled this happened. Sure, I feigned shock and disappointment, but in reality, I liked it that Alan was getting into trouble like most ten-year-old boys. He also learned a life-lesson about appropriate behavior and it opened the door for us to discuss other social dos and don’ts and the consequences for his actions.
As parents of children with visual impairments, we are often overly concerned that our kids have “perfect” behavior so we structure their lives until they become little robots unable to think for themselves. But how will they learn to live in the real world and react to everyday situations if they are not getting into a little trouble when they’re young? So take a moment to savor the rough days. Secretly try to enjoy their independent acts of mischief. And make those socially inappropriate actions into learning opportunities for life.
Have any idea or tip that can help other parents? Please drop me a line at Betsy@tfrr.org and we’ll try to get it in our next edition.

Is this the year you make a difference?
By Amber Purpura
amber@tfrr.org
I am going to let everyone in on a little secret. The first time I decided to participate in WALK With a VISION walk-a-thon I was scared to death. I thought I was going to be the only person to show up at my walk. I was so surprised when I ended up raising over $15,000 and having over 200 people come. I want you to ask yourself to think about if you are ready to make a difference. We need to come together as a whole and raise funds for the foundation that is committed to funding medical research, public awareness, and family education.
I know that all of you have had a friend, family member, or neighbor ask you what they can do to help. Yes, I know what you are thinking, “I don’t know how to set up a fundraiser, I have never done anything like that, how much could I possibly raise?”
We have new software that will allow each family to customize your personal web page and invite family and friends to visit it and support your efforts with donations. And my job is to help you!
Here is a list of families that have committed to joining us in fulfilling our mission. Thank you for all your hard work and stepping up to make a change. If your name is not on the list and you want to hold a Walk – please email amber@tfrr.org or call me at 630-978-0547. Together we will see a difference!
Amber Purpura is Communications Director of FRR. You can contact her at 1-630-978-0547 to receive information on fundraising activities for FRR.

2007 FRR Fundraisers
Adams Yearly Membership Drive - State College, PA
Amodeo Yearly Membership Drive - Dunellen, NJ
Best Walk-a-thon - Portland, ME
Bruggemann Dinner Event - West Babylon, NY
Cornell 5th Annual LCA Triathlon - Lake Geneva, WI
Drury Golf Outing - Glastonbury, CT
Frommer Purse Party - Highland Park, IL
Gruszka Golf Outing - Grand Island, NY
Johansen 3rd Annual Walk-a-thon - Tualatin, OR
Kocheran Social Party - South River, NJ
Koren Walk-a-thon - Colorado Springs, CO
Miller Walk-a-thon - Medina, OH
Moncman Golf Outing - Center Valley, PA
Moncman Walk-a-thon - Center Valley, PA
Moncman Lift-a-thon - Center Valley, PA
Nutt Beef and Beer Social - Turnersville, NJ
Nutt “Old Cell Phone” Donations - Turnersville, NJ
Pennington “Strut Your Mutt” Dog Walk - Cincinnati, OH
Purpura Walk-a-thon - Naperville, IL
Rankine Walk-a-thon - Warner Robins, GA
Rockey Walk-a-thon - West Milford, NJ
St. Arnaud Various Local Events - LaGrange, IL
La Grange Highland Women’s Club, LaGrange Highland, IL
Apex Oil Charitable Foundation - Clayton, MO
Seed Walk-a-thon - Alberta, Canada
Special Kids Network Tennis & Golf Outing - Deerfield, IL
Super Bowl Fundraiser - Chicago, IL
Swenson Fundraiser - St. Paul, MN
Walker Fundraiser - Heber City, UT
Arcilia/Villigran Walk-a-thon - Scotch Plains, NJ

GRANDMOTHERLY COMMENTS: By Ronnie Schwartz
Editor’s note: Sharing grandparenting experiences can be enlightening and helpful as we all continue to find ways to bond with our children and grandchildren who are blind. We invite you to participate in this space in forthcoming newsletters by contacting Sally Lewinksi at sally@tfrr.org
My husband Alan and I were fortunate to participate in a meeting with 25 fellow- grandparents attending the Cleveland FRR conference in July, 2006, where we shared many common feelings and experiences. We realized that for most of us, the reaction to the news of a grandchild’s blindness was initially shock, disbelief and often denial, coupled with a natural concern for our children’s adjustment to this major turn of events enveloping their marriage, impacting other children in the family, and forcing them to forge a new path in child-rearing that was unexpected, unbargained for and intimidating.
I thought it might be helpful to recount some of the many positive experiences my husband and I have enjoyed with our blind and handsome grandson Alan Brint, who is now ten years old.
For those of you who are new to the experience of grandparenting a baby who is blind, I encourage you to attend and watch some of his/her therapy sessions. It became fascinating ten years ago to watch Alan, go from being frightened, crying and uncooperative to cooing with pleasure as he learned to master the feats of clapping his hands, touching his toes, rolling over, and later doing a somersault. I remember him being fascinated with pulling big plastic alphabet letters out of a bag, feeling them, identifying them, and then throwing them across the room (which gave him even more pleasure when he learned that was a big no-no). We were not just fascinated but also took great pride in each accomplishment that in a sighted child we would have taken for granted.
Alan is now in the fourth grade of his neighborhood school, and continues to delight and amaze us with his development, albeit with some extra coaching along the way. His brother Zack walked him to school until Zack moved on to middle school; now Alan hooks up with four other kids at the corner and they all walk the five blocks together as friends.
Spending time alone with Alan is special and made easier now that his older sister Karly has taught Alan to enjoy many card games. With Braille cards we can engage him in a game of cribbage, Uno or war. We enjoy listening to him play the piano. Sometimes these activities often require some negotiating, as Alan likes to control the situation by setting down specific ground rules such as “I don’t practice piano on Sunday”, or “I’ll only play one game, but not now.” We come back with some ground rules of our own. For instance, when playing monopoly (in Braille form) I insist on rolling the dice when it’s my turn, and on making my own moves (he would prefer to take both of our turns). Another game we all enjoy is to take turns scrambling letters in a word for the other to guess. (He does it in his head, I do it on paper.) Or, using Scrabble letters, we used to take turns picking seven letters and making a word that would give the most points.
Exploring the mall is usually a successful outing. We drive to the mall of Alan’s choice and while heading for the food court we figure out what each store sells (shoes, perfume, books) by feeling or smelling, and ride the escalator several times. One time Alan’s brother Zack, a very responsible 13-year-old, rode (3 miles) with Alan to the mall on their tandem bicycle (with parental permission), with Alan doing his share of the pedaling. I was glad I found this out after the fact, but on second thought I realized how liberating this must have been for Alan.
My husband and I appreciate the importance of minimizing Alan’s blindness and maximizing his great potential by doing normal activities in and out of the house, but we are still working on his being considerate of the needs of others both in play and in ordinary activities. His grandfather encourages Alan to explore his feelings, which will help him develop social skills and not just live in his own world of facts.
Ronnie and Alan Schwartz are the parents of Betsy Brint, and one of the main reasons that the Foundation for Retinal Research exists today to help in LCA research and activities for parents and their children.

Patrick St. Arnaud debuts at Wrigley Field!
By Lori St. Arnaud
On May 5 we decided to go to Wrigley Field to lend some support to the LCA booth outside Wrigley Field. We had Mirielle while Patrick stayed at home with his Great Aunt Kathy & Uncle John.
Right when we got there the people manning the booth literally had everything all packed up in boxes and walking a way. We stopped them and said we wanted to buy a few bracelets and that our two children have LCA. They were very nice and said they would see if they could get us into the stadium to see the booth inside.
Next thing you know we were inside Wrigley at the booth. We met several volunteers from Sacramento who know Derrek Lee and do work for his foundation.
Everyone was very kind and compassionate about the cause.
We were there for about five minutes when I looked over at this 7-foot banner that says ‘Play for LCA’ and lo and behold their was Patrick’s picture!
We were surprised and excited. All the volunteers were, too. It was great to point him out, as well as Nicki, Alan and Fran from Italy. It was a great moment for us.

Lee and Cub teammates spread word about LCA
CHICAGO -- Michael Barrett and Ryan Dempster have joined Cubs teammate Derrek Lee in the fight against Lebers Congenital Amaurosis, a rare genetic eye disease, and on May 5, fans joined in the battle.
Lee’s 1st Touch Foundation, along with Chicago Cubs Charities, challenged fans to pledge money for every home run Barrett hits or every save Dempster picks up, or by simply making a contribution in the fight to cure LCA. Lee’s 4-year-old daughter Jada was diagnosed with the disease last year and is partially blind in one eye.
Fans could buy red “Believe the Unseen” bracelets to support Project 3000, a program launched by Lee and Boston Celtics CEO and co-owner Wyc Grousbeck to find a cure for LCA. The group is trying to locate the 3,000 people believed to suffer from the disease and get them tested.
“We’re just trying to get the word out and the awareness,” Lee said. “Anything we can do is good.”
Entering Saturday night’s action, Lee was leading the National League in hitting, has reached base safely in all 28 games this season and has a 13-game hitting streak. His efforts in the fight against LCA are making an even bigger impact.
Char Schwabero, who came to Saturday’s game from Naperville, Ill., heard about Lee’s daughter last year, and said she was more than happy to support the cause.
“Anytime they can get more money for research and help find a cure so [Jada] doesn’t go blind is great,” Schwabero said. “I know it’s a good cause.”
Two tables were set up at Wrigley Field on Saturday -- one at the corner of Addison and Sheffield Streets, and the other inside the main entrance -- so fans could receive information about LCA and donate to Project 3000.
“This is the first time LCA has ever been exposed like this,” said Heather Scherber, development associate for the 1st Touch Foundation. “It’s never been put in front of an audience this big. It’s the first time that it’s ever getting national exposure, and so it is an absolutely groundbreaking [experience].”
Project 3000’s goals are to identify everyone with LCA, offer affordable genetic testing, provide information about LCA and other rare eye diseases, and raise funds for LCA research. Lee and Grousbeck, who also has a child that suffers from LCA, teamed up with Dr. Edwin Stone and the University of Iowa to work toward an eventual cure.
Supporting Lee and Project 3000 was an easy decision for Margaret Davison of Kankakee, Ill.
“If my daughter were ill, I’d want some help,” Davison said.
Before Lee and his teammates took the field May 5, Alan Brint, a 10-year-old from Highland Park, Ill., who has LCA, was honored with his family on the field.
“What Derrek Lee has done, and Dr. Stone, too, is bring [LCA] to the forefront and make it something that the nation is now aware of,” said Alan’s mom, Betsy Brint.

Clara Johansens’ parents raise $15,000 for FRR, LCA
By Mark and Laura Johansen
The Johansen family put together their 3rd Annual “Walking with a Vision” walk-a-thon on May 20 in Tualatin, Oregon.
Three years ago we talked with Amber Purpura about her efforts to fundraise by putting on her own “Walk-a-thon” and we thought what a great way to get our family and friends together and to raise money and awareness for our daughter Clara’s condition.
The activism gave us a strong sense of involvement toward finding a cure for Clara’s Leber’s Congenital Amaurosis. It also helped us show David and Betsy just a small token of our huge appreciation of their efforts in providing the families affected by Lebers a place to feel comfort, strength, and knowledge about this condition.
We could not have been more touched by the response we got from friends and family our first year.
They all came together to raise over $15,000 and encouraged us to continue putting this event on year after year. We were equally successful our second year. We have included a silent auction and after-walk reception with refreshments, music, face-painting and Clara’s Vision Specialist is planning to teach kids how to type their names on the Perkins Brailler again this year.
To find out more information check our own page on the website under the “Walk with a Vision” tab, then click on “Portland” for “Choose your city”. You can see pictures of Clara and our family and friends at previous walks, and make a donation in her honor. Thanks for your continued support.

Start collecting old phones, and help raise funds for LCA research through FRR!
By Sue Nutt
Do you want to help raise money for The Foundation for Retinal Research and help the environment without costing you anything?
That’s right, it will cost you nothing! Start an “Old Cell Phone” collection program in your area! We have the wonderful opportunity to collect used, unwanted, old, even non-functioning cell phones and get money for them through a company called Eco-Cell.
You don’t need the manual, the box or the charger. You don’t need to clear out your contact information. It can even be one of those really big, old phones that seem so funny compared to the new small ones we all walk around with now. We get money for all of them, up to $15 per phone!
Your phone will be recycled in accordance with EPA regulations or refurbished & sold. Your donation may be tax deductible. 100% of the proceeds will benefit The Foundation for Retinal Research!
Some suggestions for starting a collection in your area:
• You could start a collection box at your job, your child’s school, your local church, gym or any other group or business that will allow you to do so!
• You could have a contest with family and friends to see who can collect the most phones in a specific time frame. You could give the winner a little prize or a certificate for their efforts.
• Go to your local cell phone stores and ask them what they do with their old phones. Some of the independent stores may just be throwing them away. You could help the environment and the foundation all at once!
• Another great place to talk to is a local real estate office. I am personally a REALTOR and I know myself and my co-workers typically go through at least 3 phones per year. The local office may be able to start a collection box for you.
So many people have old cell phones lying around that they don’t know what to do with it’s amazing! Just ask and you’ll see! When you have some collected, you can e-mail or call me and I’ll send you a pre-paid shipping label and all you’ll need to do is box them up and send them on their way! If you have questions you can e-mail me or call me.
SusanSchulerNutt@comcast.net/856-256-9321

Triathletes gear up for 5th annual Cornell event
By Chrissy Cornell
Although we’re still brushing off the cobwebs from a lengthy Midwestern winter hibernation, make no mistake about it, the excitement is building.
The 5th Annual LCA Triathlon Fundraiser is right around the corner. On June 24, 2007, our family will participate in the Bigfoot Triathlon in Lake Geneva, WI, as part of an effort to generate fundraising dollars for LCA research and awareness.
From brainstorming session to inception, this event has truly helped our family connect with each other and many others touched by LCA.
We’re so ready to swim, ride and run our way to THE finish line! for more information visit us on the web at www.tfrr.org

FRR BOARD UPDATE • David Brint
At this point, with all the talk of clinical trials , genes, stem cells and Lancelot everyone is wondering what is or can be done for each form of LCA. With the help of Dr. Jerry Chader, below is a summary of the current advances in various areas of the science. Each treatment is most likely predicated on whether an individual has living photoreceptors nuclei. For every form of LCA this differs by the individual. Fortunately, there are ways to determine cell existence through OCT and other adaptive optics techniques. Talk to your doctors for direction.
Remember that five years ago this article would consist of very preliminary retinal chip technology only. The promise of these and other treatments give us a great cause for hope.
Gene Replacement Therapy is the replacement of a defective, mutated gene with a normal copy of that gene. For example, if the RPE65 gene is mutated in RPE cells in some LCA patients, Gene Therapy techniques can be used to supply a normal copy of the gene that will make a normal, functional RPE65 protein. Studies in this regard on LCA animal models have been very successful. A Clinical trial with two LCA patients is now underway in London England under the auspices of Dr. Robin Ali. Two similar clinical Trials are set to start in the USA at the University of Pennsylvania in the near future. This form of treatment will be applicable to all types of LCA if the gene mutation is known and if viable photoreceptor cells remain.
Pharmaceutical therapy is the use of an agent (natural or synthetic) that will slow down the course of photoreceptor degeneration. Many such agents have been uncovered, some like the agent CNTF have been found to be effective in animal models of RP. A Clinical Trial using CNTF is in progress (phase 2) sponsored by the company Neurotech. So far, results have been good. This form of treatment is applicable to all forms of LCA (and RP) but the presence of viable photoreceptor cells is essential.
Nutritional Therapy: Vitamin A therapy is yet theoretically useful to LCA patients since LCA is a form of RP. Patients should consult their Ophthalmologist before starting a vitamin A regimen. Antioxidant supplements have recently been shown to slow photoreceptor degeneration in a number of animal models of RP. Both safety and efficacy appear to be good. A Clinical trial is being planned in Spain to test a specific formulation (called RetinaComplex) for safety and efficacy in the human. Although the testing will be on RP patients, the treatment should be applicable to all LCA patients with viable photoreceptor cells. RetinaComplex is available for purchase over the internet since the ingredients are classified as “nutrients by the USFDA and are generally deemed safe for use. Patients should consult their Ophthalmologist though before use. Remember always that the heart health and eye health go hand in hand.
Stem Cell Transplantation: This is replacement therapy for those who have lost their photoreceptors. Stem cells are primitive, undifferentiated cells that have the capacity to develop (differentiate) into any cell of the body. Each of us developed as an embryo from a few such cells. Theoretically, if cells such as photoreceptor cells degenerate and need to be replaced, stem cells can be transplanted into the appropriate area in the retina and could, with proper signals, develop into mature, functioning photoreceptor cells. Importantly, stem cells have even been found in to periphery of the adult mammalian retina, giving hope that these could be harvested, multiply and be used to replace the dead photoreceptors. In this way, the problem of the use of fetal cells would be overcome. Recent work in this area of research has been encouraging. For example, the use of early progenitor cells of rod photoreceptor cells has been quite successful in transplantation studies in not only normal animals but in animals with retinal degeneration. Photoreceptor replacement in this way, however, needs more work as to the ages of the progenitor cells that are to be transplanted as there appears to be a narrow “window of opportunity” for their use. Stem cells could afford the best possible chance for sight restoration in what otherwise might be considered terminal cases of LCA, in just the last two years.
Electronic Prosthetic Devices: When all or most photoreceptor cells are dead, they can be theoretically replaced by an electronic device that brings a visual image to the remaining cells of the retina. Essentially in this technique, a small video camera placed behind the patient’s glasses will send a visual signal to a device with multiple electrodes that is implanted on the retina. This “chip” will electronically signal the remaining retinal cells which pass the signal down the optic nerve for final processing as a visual image in the brain. Multiple clinical testing has been done on different versions of the prosthetic device in research centers around the world. In Germany, for example, acute human clinical testing has begun. In the USA, an FDA-approved Clinical Trial sponsored by the company Second Sight is just about to begin. Patients in the Second Sight trial will all be RP patients but the results should be applicable to all LCA patient with advanced disease.

A Group of ‘True Visionaries’
By Abby Imrem
Walter Payton College Prep High School in Chicago, Illinois is a magnet school, drawing the best and brightest of the inner-city students to its classrooms. Every Thursday morning of first semester, 20 of these talented students met in room 118 for a special seminar course entitled “Visionaries.” Half of the students are visually impaired or blind, and the other half are sighted. While many of their classmates were studying swing dance, relaxing in yoga class or watching Latin American films, these exceptional young people chose to spend their time together, teaching each other about what life is like in their world.
“It was an opportunity to make new friends who see the world in a different way,” said Jasmine Armand, a 14-year-old freshman at Payton.
The course is a collaboration between French Teacher Abby Imrem and Teacher of the Visually Impaired Doug Anzlovar. Imrem thinks the course fills a need that has long gone ignored at Payton and in the world. “I’ve seen sighted students jumping over the canes of visually-impaired students to get around them in the hallways, and noticed that they rarely make conversations with each other in class or at lunch. I thought getting the kids together in one room would give them the opportunity to socialize and just be together, and, with some luck, begin to learn about each other.”
Some of the activities the students did together included brushing their teeth while blind-folded, playing beep baseball, and a community service project in which they worked together to Braille menus of their favorite local restaurants. One morning, Payton’s halls were dotted with visually-impaired kids guiding blindfolded sighted students around staircases and ping-pong tables. “This activity brought the phrase ‘the blind leading the blind’ to a whole new level,” said Imrem.
“I think that people who took the seminar learned a lot about what it’s like to be blind, and I hope that they will share it with someone else and they will show someone else and so on,” said Chaquita Vinson.
Classmate Lily Diego said, “It’s definitely easier and less awkward to speak about my disability now. I feel more prepared as far as letting people know about my visual impairment and my needs in the future.”
Imrem and Anzlovar plan to continue the seminar for many years, with hope that as many young people and adults as possible can become true “Visionaries.”

Rebecca DeGeorge is offering a new class called “Braille-By-Phone” a uniquely formatted distance-learning class for relatives, teachers and friends of blind children and adult Braille readers.
Rebecca has taught Braille to adults at the Lighthouse for the Blind in San Francisco and for the Earle Baum Center of the Blind in Santa Rosa California. She is also a life-long user of Braille.
DeGeorge is the Founder & CEO of Write Spirit Coaching and her business specializes in coaching people undergoing life and career transitions. Visit www.write-spirit.com for more information on the class.

--end--

CEP290 patients retain healthy retinas and visual brain!!!

2007-06-09T00:09:00.000+02:00

Hum Mutat. 2007 Jun 6; [Epub ahead of print]

Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: Implications for therapy of Leber congenital amaurosis.

Cideciyan AV, Aleman TS, Jacobson SG, Khanna H, Sumaroka A, Aguirre GK, Schwartz SB, Windsor EA, He S, Chang B, Stone EM, Swaroop A.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.

Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness.

Abstract of article on LCA5 discovery

2007-06-05T23:49:00.000+02:00

Nature Genetics
Published online: 3 June 2007 doi:10.1038/ng2066

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis

Anneke I den Hollander1, 16, Robert K Koenekoop 2, 16,
Moin D Mohamed 3, 4, 16, Heleen H Arts 1, 16, Karsten Boldt 5, 6, Katherine V Towns 3, Tina Sedmak 7, Monika Beer 5,6, Kerstin Nagel-Wolfrum 7, Martin McKibbin 3, 8, Sharola Dharmaraj 4, Irma Lopez 2, Lenka Ivings 3, 9, Grange A Williams 3, Kelly Springell 3, C Geoff Woods 10, Hussain Jafri 11, Yasmin Rashid 12, Tim M Strom 5, 6, Bert van der Zwaag 13, Ilse Gosens 1, Ferry F J Kersten 1, Erwin van Wijk 1, Joris A Veltman 1, Marijke N Zonneveld 1, Sylvia E C van Beersum 1, Irene H Maumenee 14, Uwe Wolfrum 7, Michael E Cheetham 15, Marius Ueffing 5, Frans P M Cremers 1, 16, Chris F Inglehearn 3, 16& Ronald Roepman 1, 16

Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that linklebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
2. McGill Ocular Genetics Center, McGill University Health Center, Montreal, Canada.
3. Section of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
4. Department of Ophthalmology, St Thomas' Hospital, London, UK.
5. Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, Germany.
6. Institute of Human Genetics, Technical University Munich, Munich, Germany.
7. Institut für Zoologie, Johannes Gutenberg University, Mainz, Germany.
8. Eye Department, Chancellor Wing, St James's University Hospital, Leeds, UK.
9. Eye and Nutrition Research Group, FLAVIC, National Institute for Research on Agronomy, Dijon, France.
10. Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
11. Gene Tech Lab 146/1, Shadman Jail Road, Lahore, Pakistan.
12. Department of Obstetrics and Gynaecology, King Edward Medical University, Lahore, Pakistan.
13. Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
14. Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
15. Division of Molecular and Cellular Neuroscience, Institute of Ophthalmology, University College London, London, UK.
16. These authors contributed equally to this work.

Taken from the journal's web site at
http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng2066.html

Read more on this exciting news on the Foundation Fighting Blindness site at
http://www.blindness.org/research.asp?id=310&type=2,%203,%204,%205,%206

New LCA gene identified, and CEP290 trials to be launched in the near future!

2007-06-04T12:25:00.000+02:00

This is all too exciting. Dr. Koenekoop and the same international research team that discovered CEP290 has just identified a new gene causing LCA, called LCA5. Its role in the retina seems to be similar to that of CEP290, causing ciliary disfunction in the photoreceptors. This discovery was just announced! Dr. Koenekoop thinks that clinical trials for both CEP290 and LCA5 might be launched in the near future.

I’ll try to find more. Meantime, read the story at
http://www.sciencedaily.com/releases/2007/06/070603215217.htm

Sight can be restored in older people blind from birth

2007-05-22T20:37:00.000+02:00

Contrary to what most scientists believed in the past, there is now evidence that sight can be restored in older children and even adults who are blind from birth. The case of an Indian woman, who "learned how to see" after her cataracts were removed at age 12, is proof of this. Pawan Sinha, associate professor of neuroscience at M.I.T. and co-author of a paper describing the case published in the December 2006 issue of Psychological Science, says that "There is a critical period for perfect acuity, but there is not a critical period for learning to do complex visual tasks."

Read the full article on the Time web site at
http://www.time.com/time/magazine/article/0,9171,1592846,00.html

Cat model for CEP290 LCA

2007-05-18T13:28:00.000+02:00

An article just published in the Journal of Hewredity reports the identification of a cat pedigree carrying a mutation in the CEP290 gene. These cats exhibit retinal degeneration transmitted with a recessive pattern. Until this discovery, only a mouse model for CEP290 was available, the RD16 mouse. The identification of a large animal model for human retinal blindness offers considerable promise in developing gene-based therapies.

Derrek Lee spreads awareness about LCA

2007-05-06T11:20:00.000+02:00

Cubs first baseman spearheading campaign to raise donations
By Marc Zarefsky / MLB.com
CHICAGO -- Michael Barrett and Ryan Dempster have joined Cubs teammate Derrek Lee in the fight against Lebers Congenital Amaurosis, a rare genetic eye disease,and on Saturday, fans joined in the battle.
Lee's 1st Touch Foundation, along with Chicago Cubs Charities, challenged fans to pledge money for every home run Barrett hits or every save Dempster picksup, or by simply making a contribution in the fight to cure LCA. Lee's 4-year-old daughter Jada was diagnosed with the disease last year and is partiallyblind in one eye.
Fans could buy red "Believe the Unseen" bracelets to support Project 3000, a program launched by Lee and Boston Celtics CEO and co-owner Wyc Grousbeck tofind a cure for LCA. The group is trying to locate the 3,000 people believed to suffer from the disease and get them tested.
"We're just trying to get the word out and the awareness," Lee said. "Anything we can do is good."
Entering Saturday night's action, Lee is leading the National League in hitting, has reached base safely in all 28 games this season and has a 13-game hittingstreak. His efforts in the fight against LCA are making an even bigger impact.
Char Schwabero, who came to Saturday's game from Naperville, Ill., heard about Lee's daughter last year, and said she was more than happy to support thecause.
"Anytime they can get more money for research and help find a cure so [Jada] doesn't go blind is great," Schwabero said. "I know it's a good cause."
Two tables were set up at Wrigley Field on Saturday -- one at the corner of Addison and Sheffield Streets, and the other inside the main entrance -- sofans could receive information about LCA and donate to Project 3000.
"This is the first time LCA has ever been exposed like this," said Heather Scherber, development associate for the 1st Touch Foundation. "It's never beenput in front of an audience this big. It's the first time that it's ever getting national exposure, and so it is an absolutely groundbreaking [experience]."
Project 3000's goals are to identify everyone with LCA, offer affordable genetic testing, provide information about LCA and other rare eye diseases, andraise funds for LCA research. Lee and Grousbeck, who also has a child that suffers from LCA, teamed up with Dr. Edwin Stone and the University of Iowato work toward an eventual cure.
Supporting Lee and Project 3000 was an easy decision for Margaret Davison of Kankakee, Ill.
"If my daughter were ill, I'd want some help," Davison said.
Before Lee and his teammates took the field Saturday, Alan Brint, a 10-year-old from Highland Park, Ill., who has LCA, was honored with his family on thefield.
"What Derrek Lee has done, and Dr. Stone, too, is bring [LCA] to the forefront and make it something that the nation is now aware of," said Alan's mom,Betsy Brint.
"When I walked into the stadium, I saw a total stranger wearing a 'Play for LCA' T-shirt, and I almost burst into tears," Betsy Brint said. "This has beensuch a quiet disease, such a rare disease that people don't know about it, and I've spent the last 10 years trying to educate people and bring awarenessto it."
Barrett and Dempster got things started this spring. In addition to an initial $50,000 donation by each player, Barrett will donate $10,000 for every homerun he hits, while Dempster will give $1,000 for every save.
"Everybody here knows, and everybody who's involved knows what a tremendous cause it is, and hopefully one day we can find a cure," Dempster said afterconverting his seventh save of the season. "I'm just out there trying to do my part and get a little more money for that pot."
Fans could also "Play for LCA" and donate money to Project 3000 based on Barrett's home run total and/or the number of Dempster's saves.
Stone, who also was honored in the pregame ceremony, was more than pleased with the promotional activities and fan reaction at the game.
"Most of the patients that come to see me have been told at least once, if not several times before I've seen them, something equivalent to, 'I'm sorry,there's nothing we can do,'" Stone said. "If you stand around this table and look around, you don't get the 'There's nothing you can do' feeling. You seeall these people walking up to this booth and putting on a wrist band, there is something you can do.
"For those of us that have been working on inherited eye diseases for a long time, to have this degree of energy injected into the process is an extremelyexciting thing for us," Stone said.
The Cubs' Minor League affiliates are also helping raise money and awareness for LCA. As part of Project 3000 Night on May 12, the Iowa Cubs Foundationwill donate $1,000 for every home run hit by an Iowa Cub during the game and $100 for every strikeout recorded that evening.
There will also be a silent auction held at the game, where fans will be able to bid on jerseys, baseballs and bats signed by Lee, Carlos Zambrano, AlfonsoSoriano and Ryne Sandberg, as well as other current Chicago and Iowa Cubs players. All of the proceeds will go to Project 3000.
"In order for us to achieve our goal of curing this disease, it is going to have to be a societal-based effort," Stone said. "It isn't going to be one singlebreakthrough. It's going to be constant effort with optimistic people believing this can be overcome and just not willing to take no for an answer."
For more information about supporting Project 3000, visit http://www.helpproject3000.org
For information about genetic testing for people with LCA, visit http://www.carverlab.org/project3000
For information about Lee's 1st Touch Foundation, visit http://www.1sttouch.org

Marc Zarefsky is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.

History in the making: RPE65 trial has begun!

2007-05-01T18:38:00.000+02:00

The news we've all been waiting for. Thanks a million to Andrew for posting this terrific info on the LCA mailing list, along with the link to the BBC story below. RPE65 gene therapy human trials are underway in London! Check it out at
http://news.bbc.co.uk/1/hi/health/6609205.stm

The trials in the US should also begin shortly, if they are not already in progress. Whatever their results, this is history in the making...

Update on upcoming RPE65 trials

2007-04-23T21:33:00.000+02:00

Hello! We have good news. The RPE65 human clinical trials, of which we’ve been talking about for a long time, are scheduled to begin any day. Seems like they’ve been postponed a bit, but now we’re apparently there. The Foundation Fighting Blindness has just published the audio presentations given at the Day of Science Conference this year, which includes one by Dr. Jean Bennett, who is directly involved in the planning of one of these trials. 3 trials are going to begin shortly: 2 in the US – one for adults and one for children – and one in the UK. Other speeches include the discovery of CEP290, the genetics of retinal diseases, the potential of stem cell transplantation, and much more. You can listen to the presentations, or read summaries at
http://www.blindness.org/content.asp?id=476

Fran

The Foundation for Retinal Research newsletter, January 2007

2007-03-22T18:04:00.000+01:00

FRRVisions
The newsletter for families and supporters of The Foundation for Retinal Research
JANUARY, 2007
Baseball star joins FRR team
Cubs first baseman Derrek Lee first announced the launch of Project 3000 in late September, there has been great excitement and a flurry of activity among doctors and scientists who care for patients with Leber Congenital Amaurosis. And, Lee’s 3-year-old daughter, Jada, who lost her vision in one eye and prompted the effort, is still getting mail, prayers and support. Someday, they hope to find a cure. Lee teamed up with Boston Celtics owner Wyc Grousbeck to create Project 3000, a foundation to fight LCA. The goal is to provide state-of-the-art genetic testing for every man, woman and child who has LCA. People are urged to contact Project 3000 for more information. “We have already had tremendous interest in this project from all over the world,” said Dr. Edwin Stone, a professor of ophthalmology at the University of Iowa Carver College of Medicine and the scientific director of Project 3000. “In the first day alone, the Project 3000 Web site received thousands of hits, and Cubs fans and Celtics fans began sending in support. ”For example, one fan, who lives in Japan, first met Lee more than 20 years ago when his father played baseball there. He put a Derrek Lee Cubs jersey up for auction and sent the proceeds to fund the research effort at the foundation.“She’s doing great,” Lee said on Monday of his daughter. “You would never know.”Lee and his wife, Christina, are able to deal with their daughter’s partial blindness better after meeting 9-year-old Alan Brint, who also has LCA.“They wondered how children who are blind function,” said David Brint, Alan’s father and the director of the Foundation of Retinal Research. “When they got to meet my son, you could see the light in their eyes. ”Young Alan is a talented pianist and has perfect pitch, said his father. The boy, who’s also a Cubs fan, can play whatever he hears.“[Alan] plays games, has a good sense of humor and he functions around the house,” said Brint, who lives in the Chicago area. “I’m not saying it’s easy -- it’s a lot of work and it’s scary. But I think it calmed [the Lees].“You start entering a world and learning what you can do,” Brint said. “You get enough help and say, ‘OK, I can do this.’ It takes a lot of therapy and help and love. ”The Lees admitted meeting Alan helped ease some of their fears.“You see someone else going through it and they’re fine,” Lee said. “It’s comforting to know it will be OK. ”Their fight continues to find a cure. Since Project 3000 was announced, Stone said that interest has been high among doctors who care for LCA patients. For example, Dr. John Kitchens, a retina specialist in Kentucky, has already organized his partners to help identify all of the patients in that state afflicted with LCA. Similarly, Dr. Richard Weleber and his staff at the Casey Eye Institute in Portland, Ore., are helping to design a patient questionnaire that will help the team identify patients with LCA from among the tens of thousands of patients who, for a number of other reasons, first experienced severe vision loss during their childhood. In the Carver Laboratory at the University of Iowa, several additional personnel have been hired and some new robotic instrumentation has been installed to help keep up with the increased number of genetic tests being ordered. “Working together, sports fans, professional athletes, patients, parents, doctors and research scientists are already making terrific progress in our understanding of LCA,” Stone said. “And with all this momentum, we are looking forward to even greater things in the coming year.” Lee is determined to do whatever he can, and may go with Brint to attend the Foundation for Fighting Blindness “Day of Science” event in Orlando, Fla., in January, when researchers gather to talk to constituents. There’s strength in numbers, Brint said, and Project 3000 is a huge step in finding people affected with LCA and getting them tested. “This project that [Lee’s] doing will have an enormous impact,” Brint said. “A lot of people had been misdiagnosed. There are eight, 10 different genes that can cause this. We want to find out people who have this diagnosis, and we want to do gene screening to find out which genes are involved. “This is a project we’ve been trying to do in modest ways for half a dozen years. This will make it happen in short order and the information will be enormously valuable.”

FAMILY TO FAMILY
Our role as parents is to give our children the tools needed to meet their full potential in life and be happy. The role of our children is to present us with challenges every step of the way! Most families have it pretty easy until the dreaded teenage years (ask any parent of a teenager), but as a parent of a child with LCA, we were faced with serious challenges from the beginning. When our son was diagnosed almost 10 years ago, we had just gotten our first email address and had just begun dabbling on the internet. (Hard to imagine that only 10 years ago most families didn’t have internet!) We tried searching for families in a similar situation as ours but had a tough time finding them. We hunted for researchers studying Leber’s, but found none. We needed to learn more about this strange thing called LCA but couldn’t find articles written in layman’s terms. Though the moral support we got from our family and friends was incredible; we needed more. The Foundation for Retinal Research began as a way to fund research for LCA but it has become much more. FRR now fills the gap that was so large ten years ago. Families are now able to immediately get information about LCA (written in a language they understand), they are able to connect with other families all over the world who are raising children with LCA, they are able to meet biannually at FRR sponsored conferences and, many are even able to find out the gene that has caused LCA in their child. Armed with these tools, we are able to face the challenges of raising a child with a visual impairment and involve our friends and family members through fundraising to help find out even more about this disorder known as Leber’s Congenital Amaurosis. The biggest problem now…dealing with our teenagers! Thank you all for adding to our support network. Together, we will help our children reach their full potential! David & Betsy Brint

ince Cubs first baseman Derrek Lee first announced the launch of Project 3000 in late September, there has been S

Hold a fundraiser for FRR
Soon, you will have little excuse NOT to host a “Walk-With-A-Vision” fundraiser for the Foundation for Retinal Research. The FRR leaders are about to launch new additions to the Foundation’s website (www.TFRR.org) that will allow anyone to host a “Walk-With-A-Vision” event in their hometown. The new website features will allow people in your specific community to log onto the site and register “online” to walk in the “Walk-With-A-Vision” or sponsor a walker. “The new feature will let someone who wants to walk in a “Walk-With-A-Vision” to sign up on our website, then send out emails to all their friends sending them back to the website to sign up to sponsor them in the “Walk-With-A-Vision,” said Amber Purpura, Director of Communications for FRR, and parent of Nicki, age 7 and an LCA patient. The new registration feature will allow walkers and sponsors to sign up and pledge their support, and it will also help to invoice the sponsors quickly and easily .“It takes a lot of the paperwork and the headache out of holding a “Walk-With-A-Vision” event,” Pupura said. “Someone can email 30 to 100 or more of their friends, family and co-workers to sign up to sponsor them, instead of calling or visiting.” The process to hold a “Walk-With-A-Vision” in your community is easier, too (see graphic below). The goal is to have 10 or more of the “Walk-With-A-Vision” events in 2007, Purpura said.Contact Purpura at FRR offices, or email her at amber@TFRR.org.

Here’s how to do you own ‘Walk-With-A-Vision’
STEP 1: Call Amber Purpura at FRR and get an event guide with complete instructions on how to hold your event, and get your personalized webpage set up to take pledges and donations, and to register walkers.
STEP 2: Pick a date and a location for your event
STEP 3: Email, call and contact as many of your family mem-bers, friends, co-workers, neighbors and acquaintances and ask them to sign up on the website to walk and/or pledge
STEP 4: Hold your event and raise money to fight LCA!

Betsy’s Corner
If you’re like me, you are always looking for better ways to help you blind or visually impaired child in the classroom. Amber Purpura and I came across this great article about how to best work with your child’s classroom aide. We’ve reprinted the gist of the article here. Enjoy! Helping or hovering? What is the effect of educational aides on students with visual impairments? An article published in Disability Solutions magazine says that sometimes when the role of the paraprofessional is unclear, they may actually be a barrier to student learning. It is helpful if the paraprofessional continually asks the following question while assisting a student: “Is this something a classmate, buddy, or peer tutor could be doing rather than me? Can this student be successful with less assistance overall?” Often parents will advocate for the presence of a full-time paraprofessional out of concern for their child’s success. It is important to discuss the role of the paraprofessional several times each year. If a student can be successful in the classroom once peer supports are developed, the role of the paraprofessional changes. For some students the paraprofessional will continue to be a necessity. However, their direct interaction with the student should lessen over time as natural supports and accommodations are developed and the student learns the new classroom routines. •Consider hiring and assigning assistants for a particular classroom versus an individual student. •Decide as a team (school staff, parents and student) when it is appropriate for an instructional assistant to provide close proximity support to a student and when to facilitate natural support from the environment, other adults and peers. •Provide information and awareness training to school staff, teachers and parents on the effects of adult proximity on students with disabilities. •Give instructional assistants training and information on how to fade prompts and supports and facilitate the students’ use of independent skills and natural supports in the environment. •Teachers and administrative staff should provide ongoing evaluation and supervision to instructional assistants supporting students with disabilities. Have any idea or tip that can help other parents? Please drop me a line at Betsy@tfrr.org and we’ll try to get it in our next edition.Page 2

STORIES OF HOPE: Sela Cornell’s parents hopeful about LCA cure
Mike and Chrissy Cornell were overjoyed with the birth of Sela, but within the first few months of her life noticed a lack of visual responsiveness and unusual roving eye movements. Initially doctors weren’t concerned about this condition, known as nystagmus, but when the condition persisted, they sent Sela for numerous tests. At first they suspected a brain tumor, and later focused on the retina. Baby Sela was only six months old when the diagnosis came: Leber Congenital Amaurosis. “You are never prepared to hear something like that as a parent,” says Mike. “We didn’t know where to turn, and the information on LCA that was readily available was sparse.”
Needing the support of family and friends, the Cornells packed up and moved back to Chicago. “It was a difficult time for us,” says Chrissy. “We needed time to grieve. And although we set out right away to get Sela the special help she needed, we felt overwhelmed and alone.” Eventually the Cornells found solid ground, in part because they met David and Betsy Brint, who also had a son with LCA and had started the Foundation for Retinal Research a few years earlier. “David and Betsy were so open and warm and invited us into their home,” says Chrissy. “After we left their house I remember thinking, ‘they were laughing and joking around—they are such a happy family.’ Meeting the Brints gave us that sense of support we had been missing.” The Cornells decided that they wanted to do whatever they could to help fund research and awareness efforts for LCA. They started a fundraising triathlon, raising money from family and friends. “Once we started doing something positive, we began to feel more connected to what was going on in the LCA community,” says Mike. “The triathlon provided a constant reminder that there are people out there who want to help support Sela, her family, and others who are in the same boat.”
Sela, now four and a half is learning Braille and has started using a mobility cane, which she decorates with little charms and colorful tape, and proudly tells friends and strangers that it “helps her see.” “We are so proud of Sela and thankful for the network of information and support the FRR has provided”, says Mike, “and thanks to the research advances in the past few years we are very hopeful about a cure. It’s no longer a question of ‘if’ a cure will be found but when.”

TFRR salutes its upcoming fundraisers for 2007
Mike and Chrissy Cornell have not only devoted a lot of their time to helping The Foundation for Retinal Research, they have also raised a substantial amount of money for re-search projects funded by FRR. The Cornell’s have organized triathlons that have raised more than $50,000 in 2006. Fundraisers scheduled for 2007 are listed below. If you would like to host a fundraiser, please call Amber Purpura at 1-630-978-0547. Thanks to everyone who has helped!
Amodeo Yearly Membership Drive
Adams Yearly Membership Drive
Best Walk-A-Thon
Bushland Walk-A-Thon
Bruggemann Dinner Event
5th Annual Cornell Triatholon
Gillaspie Walk-A-Thon
Gruszka Golf Outing
3rd Annual Johansen Walk-A-Thon
Kocheran Social Party
Koren Walk-A-Thon
Miller Walk-A-Thon
Moncman Golf Outing
Moncman Lift-A-Thon
Moncman Walk-A-Thon
2nd “Nutt” Beef/Beer Social
Rankine Walk-A-Thon
Rockey Walk-A-Thon
Special Kids Network
Super Bowl Raffle
St. Arnaud Various Events
Raffles
Sporting Events
Auctions
Seed Walk-A-Thon
Swenson Fundraiser
Pennington “Strut Your Mutt” Walk
Purpura Walk-A-Thon
Walker Fundraiser
Zacknoun Walk-A-Thon

Interested in hosting a Fundraiser for FRR? Please contact Amber Purpura at 1-630-978-0547.

‘FRR VISIONS’ is the quarterly wewsletter for the Foundation For Retinal Research.
We hope to spotlight families and research projects. If you have an idea for a newsletter item, please contact Amber Purpura at 1-630-978-0547. We appreciate your comments!

CHECKLIST: TESTING FOR LEBER CONGENITAL AMAUROSIS
STEP ONE: WHEN LCA IS SUSPECTED: TESTING BEFORE AN LCA DIAGNOSIS HAS BEEN REACHED Often, parents are the first to know that there is a vision problem in their child. In LCA, this can come early when their child does not respond in the usual manner to visual stimuli and cues. The first step after this, of course, is to take the child to their physician - Pediatrician, Ophthalmologist, etc. Most often, a diagnosis can be made from the initial eye exam by an Ophthalmologist. The main sign is very low vision early in childhood. Other signs might be nystagmus (wandering eye), lack of proper pupil response or eye rubbing. The Ophthalmologist might consider some specialized testing to assess the situation. One such test might be Electroretinography (ERG). Since the retina is neural and part of the Central Nervous System, the retinal neurons produce characteristic electrical patterns that can be measured. The normal retina produces a fairly standard ERG pattern that changes under disease conditions. In LCA, the ERG signal is usually markedly diminished or even extinguished. Along with the ERG test, a general physical exam and probably a hearing exam will be performed. These are done to rule out other conditions which can masquerade as LCA. As better explained in Step Two, these are usually not necessary but might be needed in special cases. STEP TWO: RULING OUT OTHER CONDITIONS As mentioned above, occasionally, the eye signs of LCA can be caused by other disease processes. When this is suspected by the Ophthalmologist, the following other tests can be performed that rule out the other conditions. Again, it is important to point out that these tests are usually not needed but only indicated if the Ophthalmologist suspects that LCA may not be the primary diagnosis.1) Physical Examination: A complete physical examination can be conducted usually by the primary care physician to rule out other medical issues as best as possible. Specific questions are asked that elicit signs and symptoms that may indicate the involvement of systems other than the eye and vision. The Foundation for Retinal Research has prepared this document to assist families of children with Leber Congenital Amaurosis (LCA). Use it to determine what tests should be performed before an LCA diagnosis has been reached and, then, after an LCA diagnosis has been confirmed.

FRR BOARD UPDATE
David Brint
The Cleveland LCA Conference last July was a milestone for the Foundation for Retinal Research. It was great to see so many families eager to move the mission of the FRR forward rapidly. Right after the conference, several parents met with us for a strategic planning session. We would like to recognize Dave Bushland, Lee St. Arnaud, Mike Cornell, Tim Pennington and Amber Purpura. The strategic planning session helped us re-define our mission, evaluate our administrative needs and outline our fund-raising goals for the coming years. A special thanks to Chrissy and Mike Cornell for being sounding boards and consistent rational thinkers in matters of importance to the FRR. Their endless time and thoughts are appreciated by us, as well as Amber. Jerry Chader, FRR’s Chief Scientific Officer, along with the help of Lee St. Arnaud, spent endless hours creating a Clinical Workup for newly diagnosed LCA patients (Page 4-5). No longer will a newly diagnosed family have to spend months trying to figure out what to do. As a result of the strategic planning session, an associate board focused on fundraising will be established. That Board will guide the efforts of our grassroots fundraising and will direct any national event efforts. We are pleased to announce that we have hired Sally Lewinski as a full time office administrator. This will free up Amber’s time to do more fundraising nationwide with all of our members. We hope that these initiatives will allow the Foundation to effectively continue to move research forward. It seems that every week some new finding occurs. We want to make our vision a reality.

SCIENCE & RESEARCH: A Path to a Cure
Dr. Jerry Chader
In a hereditary disease, the most obvious way to treat and possibly cure the disease is to replace the defective gene. This is called Gene Replacement Therapy. Over the last few months, there has been substantial progress in both Gene Therapy and the necessary steps leading to the therapy for LCA patients. Genes: LCA is not a single disease entity in that mutations in more than one gene (genotype) can lead to the physical signs (phenotype) of the disease – specifically, severe vision problems in childhood. As is obvious, knowing the identity of the gene mutated in a particular patient is basic to replacing that gene. As reported by RetNet, the premier web repository of gene information on retinal degenerations, 11 different genes are now known whose mutations can lead to recessively inherited LCA. Mutations in 2 known genes lead to dominantly-inherited LCA. Up to a few months ago, the genes identified to that time accounted for an estimated 45% of LCA cases. More recently, a mutation was identified in a new gene (CEP290) that accounts for about 20% of LCA patients. Thus, to date we know the gene mutations responsible for 60-70% of all LCA cases. Breaking news in this area is that a new gene mutation has just been identified. It is not yet known what the prevalence of this gene mutation is in the general LCA population but certainly will ultimately allow for future gene replacement in a higher percentage of LCA cases. Genotyping: Matching up a particular gene mutation with a particular patient is called genotyping. Certainly, no patient can undergo Gene Therapy without proper genotyping. Several genotyping centers are now operating, one of which is led by Dr. Ed Stone at the Carver Laboratory, University of Iowa. The lab is run in a “non-profit format” with reimbursement for only the actual costs of performing the tests. Finding the gene in some patients will be easier (or luckier) than in others, thus the cost of the testing will vary from case to case. However, the cost is relatively modest - $100-1200/patient. Along with the most direct benefit of genotyping, i.e., putting the patient in the queue for future Gene Therapy, there are secondary but yet important benefits. For example, knowing the gene mutation should allow for a more accurate prediction of the disease course in each individual. Specific mutations may be associated with a better prognosis – good news for any family with a newly diagnosed child. Gene Therapy: Once an LCA patient’s gene mutation has been confirmed, the person becomes a candidate for gene therapy. Of course, no such treatment is presently available for any of the LCA gene mutations but a clinical trial for one type of LCA is getting underway with others yet in the planning stages. The gene in question is the well-known RPE 65 gene whose mutation leads to severe visual dysfunction in early childhood. Excellent animal models with RPE65 mutations are available that have the same phenotype as in the human. Using these models, extensive preclinical work over the last 7 years has demonstrated both safety and efficacy of Gene Replacement Therapy for this condition. In fact, animals treated over 5 years ago are yet seeing very well. This gives great hope that both children and adults with the RPE65 mutation can be treated in the next few years. Thus, many of the theoretical and scientific hurtles in defining an effective and safe treatment for LCA have been overcome. It is up to us now to overcome the practical problems of uncovering sources of funding and companies willing to work on this “cure” for all genetic forms of LCA. The Mission of the Foundation for Retinal Research is finding treatments and cures for Retinal Degenerative Diseases and supporting affected families.

Amber Bobnar is new editor of “Just For Parents”
Amber Bobnar has agreed to be the lead editor of the “Just For Parents” page on the FRR website at www.TFRR.org. Amber is the mother of Ivan Kapi’i Bobnar, born June 11, 2005. Ivan was diagnosed with LCA at 13 months but Amber has been learning about LCA and blindness since Ivan was 3 months old. She is the author of many articles on her website, www.wonderbaby.org, and is always looking for fun and exciting ways to encourage Ivan and other blind babies to interact with their environment. Amber, Ivan, and dad (Esoos) all currently live in Kealakekua, Hawaii but are soon planning a long move to Watertown, Massachusetts where Ivan will attend the Perkins School for the Blind.

end

Retinal chip soon on the market

2007-02-18T19:42:00.000+01:00

The retinal chip may be on the market as early as in 2009! The US Food and Drug Administration has approved experimentation at a large scale of the new, more sophisticated version of the “bionic eye”, developed by Dr. Humayun at the University of Southern California. If these trials give the expected results, the device will be available on the market in 2 years, at a cost of approximately 300.000 dollars, or 25.000 euros. The chip will mostly benefit blind people who once had sight but it will be tried on patients blind from birth as well.
An article on this exciting news was just published in the Guardian. Check it out here.

The future looks bright!

Italian lab to fight LCA

2007-02-14T23:48:00.000+01:00

For a long time now, I’ve been trying hard to locate centers involved in gene therapy animal trials for LCA, and I was so surprised, and proud, to learn that one of them is right here in my country! The Telethon Institute of Genetics and Medicine (TIGEM) of Naples, Italy, was founded by the Italian Telethon Foundation in 1994. One of its current programs concerns the diagnosis and genetic study of inherited eye diseases, which includes LCA.

I just spoke with Dr. Alberto Auricchio, who is working specifically on gene therapy in animals. What struck me about him, along with his huge kindness and friendliness, was his enthusiasm for what he’s doing. It was wonderful talking to him! His lab is working on animal models for both LCA and RP. He’s also following closely the unfolding RPE65 human trials, scheduled to begin in a few months.
TIGEM also offers genetic screening for the LCA genes known so far, using a chip, which can greatly speed up the diagnosis if a known mutation is present.

Dr. Auricchio was so kind to tell me he’ll stay in touch for any updates. That is wonderful news! So nice to meet such a nice person, and so close to home too...

Do visit the TIGEM site. Lots of interesting, exciting stuff!
Go Napoli!

Well-written web article on CEP290

2006-10-17T23:20:00.000+02:00

I’ve come across this nice report on the discovery of CEP290. I’m pasting some excerpts here. You can find the full article on the eurekalert! website at
http://www.eurekalert.org/pub_releases/2006-10/mu-bbm100406.php

Eye Health Month is off to an exciting start, with the recent announcement by MUHC [McGill University Health Centre] researcher Dr. Robert Koenekoop and his colleagues of a breakthrough discovery in the genetics of childhood blindness. The new study identified the gene most often responsible for LCA (Leber Congenital Amaurosis), the commonest form of congenital blindness...
The disorder affects 1 in 30,000 newborns, and is currently incurable. "This is about to change, however," says Dr. Koenekoop. "Our discovery has major implications for improved screening. It also opens avenues for treatment of LCA."

...From a therapeutic viewpoint, this discovery adds another pathway for possible therapeutic manipulation and paves the way for a human gene replacement trial of a related LCA gene (RPE65) in early 2007. If this trial is successful, gene replacement therapy may not be far off.

Prior to Dr. Koenekoop's discovery, LCA had been linked to mutations in eight genes. Together, these mutations account for about 45 percent of cases. By studying members of a Quebec family affected by LCA, Dr. Koenekoop's team, which includes research associate and molecular biologist Dr. Irma Lopez, was able to identify a mutation in a gene known as CEP290. This mutation was detected in 21 percent of unrelated cases - making it one of the most common causes of LCA yet identified...

... The MUHC, in collaboration with Dr. Anneke den Hollander and Dr. Frans Cremers from the University of Nijmegen, will continue research into LCA, conducting functional studies of the CEP290 gene and screening more patients for CEP290 mutations.

Quebec is the perfect place to study genetic diseases like LCA. Quebec's population of approximately 6 million is known as a "founder population" because it can be traced back to a small number (approximately 250) of forefathers. This small gene pool provides the ideal population for the study of genetic disease. "Genetic diseases like LCA are more common in founder populations," says Dr. Koenekoop. "Our patients are enthusiastic about participating in these studies. They realize this research may ultimately lead to improved diagnosis, treatments and cures."

adapted from
http://www.eurekalert.org

Project 3000: the world of sports joins us in the fight

2006-09-29T19:52:00.000+02:00

The news is terrific. It has just been announced on Dr. Stone’s Carver Lab’s website that Chicago Cubs star Derrek Lee and Boston Celtics CEO and co-owner Wyc Grousbeck have committed their efforts towards a cure for LCA. Their lives have both been touched by this disease. The main goal of their initiative, called Project 3000, is to ensure genetic testing for all people with Leber’s within the USA, which will help understand this disorder better, identify candidates for future clinical trials, and devise treatments specific to each LCA subtype.

This is wonderful news. This will bring LCA to the attention of the world. We are at a turning point in retinal research. Clinical trials on RPE65 are about to begin, others will follow shortly after, if all goes well. The potentials are there...Research needs all the help and support it can get.

Thanks so much to these two celebrities for joining us in this race towards sight.

Check the Carver Lab’s site for more information. A side note: there is also my picture there!

Fran

Classification for Leber's Congenital Amaurosis

2006-09-21T21:02:00.000+02:00

As more and more genes causing LCA are being discovered, attention is shifted from this disorder as a whole to its subtypes, each caused by mutations in one specific gene. At the LCA conference in Cleveland, one of the speaker said that in a few years we will probably be talking about each subtype separately, and stop using a collective name for them.

Below is the classification of the 11 types of LCA currently known, with the relative gene and chromosome. This is pretty interesting because it provides some form of classification, as well as a complete and updated list of the LCA genes known to date. This information is taken from the OMIM (Online Mendelian Inheritance in Man) database, so it couldn’t be more reliable. You can find this information, plus links to each gene, at

Fran

LCA1
caused by mutation in the gene encoding retinal guanylate cyclase (GUCY2D, on chromosome
17

LCA2
caused by mutation in the RPE65 gene (RPE65, on chromosome 1

LCA3
caused by mutation in the RDH12 gene, on chromosome 14

LCA4
caused by mutation in the AIPL1 gene, on chromosome 17

LCA6
caused by mutation in the RPGRIP1 gene, on chromosome 14

LCA7
caused by mutation in the CRX gene, on chromosome 19

LCA8
caused by mutation in the CRB1 (CRUMBS) gene, on chromosome 1q

LCA10
caused by mutation in the CEP290 gene, on chromosome 12 (may account for as many as 21% of cases of LCA)

LCA11
caused by mutation in the IMPDH1 gene, on chromosome 7q

Additional loci for LCA have been mapped:
LCA5, to chromosome 6q11-q16, and
LCA9, to chromosome 1p36.

The amazing genetic screening program at Carver Lab

2006-08-05T12:22:00.000+02:00

I guess I had not fully understood the huge difference Dr. Stone’s work is making both for patients and research, until I heard his presentation in Cleveland. Carver Lab, at the University of Iowa, offers quick genetic screening for the known LCA genes for a fee (though free testing on a research basis is offered as well). The work is completely non-profit, the fee is only used to cover the expenses of the test. This is certainly great news for patients who can obtain their test results rapidly, but also for LCA research: knowing the mutation of as many patients as possible can increase knowledge about that particular gene, allows for better genotype-phenotype correlations, enables to exclude subjects with known mutations from the search for new LCA genes, and will ultimately facilitate the selection of eligible patients for future clinical trials. On top of that, the Carver Lab’s website

provides an online tracking system which allows patients to access the status of their genetic test, which I think is incredible! Dr. Stone and his colleagues perfectly understand the psychology of patients and their families, as well as the problems in LCA retinas :-). In his presentation he reiterated many times the importance of keeping in touch with patients and families, who want and need to know about the status of their genetic screening, and not simply a yes or no answer.

Genetic testing at Carver lab is done on different stages. In the first stage the most important known mutations of LCA genes are tested. If no mutations are found, the patient may opt to proceed to the second stage, where more unlikely mutations are tested, and so on with the third stage. The initial fee covers all thre stages, so if the patient or family decides to stop at stage 1 or 2, the unused money is refunded. Some may choose not to proceed to the further stages since chances to find something there is highly unlikely.

Dr. Stone’s lab also carries out research on candidate LCA genes, and studies the known genes in detail.

For further information just visit the Carver Lab's website given above. Dr. Stone’s kindness is overwhelming. He and his colleagues will certainly give you all the information you need.

Fran

News from the 4th LCA conference: couldn't be better!

2006-07-31T01:19:00.000+02:00

(edited in the following days. Thank you to all the friends who are helping me add more info)

I’m still in Cleveland for the LCA conference, and I’m so thrilled I’m going to post the latest news right from my hotel room! This is just a few points; I may add more later as more info comes to my mind. In a nutshell, it is terrific news!

The RPE65 gene therapy trials are about to begin! Dr. Jean Bennett reported on the lengthy, painstakingly hard process it takes to have a clinical trial approved, especially when it involves children. Two trials are about to be approved, one enrolling adult patients and one for pediatric subjects. They should begin in January of 2007. The whole world is waiting for the results of these trials because if they are successful, more similar trials on gene therapy will be approve, and the speed at which they can be initiated will increase exponentially!!!

Much was said about the new gene, CEP290, which somehow was the highlight of the conference. Dr. Robert Koenekoop from Montreal Children’s Hospital reported about how he and his collaborators were able to find it,mostly thanks to the participation of a large Canadian family Where 4 siblings have LCA. The CEP290 gene seems to be very common, probably accounting for over 20% of LCA cases. After learning about this gene only 3 weeks ago, Dr. Stone from Carver Lab has found mutations in this gene in a huge number of his patients, and more need to be screened. Since only common mutations in the CEP290 gene have been screened so far, it is estimated that the rate of patients carrying mutations in this gene may be even higher.
Though more research has to be done on CEP290, Dr. Koenekoop thinks that it is very likely to be involved in protein trafficking. Put simply, proteins needed for vision do not travel from the inner region of the photoreceptors to the outer segments, so the vision cycle is severely impaired. The retinas of children with these mutations seen so far exhibit retinas with normal appearance; even the retinas of adult patients don’t look bad at all! Some more good news about this gene is that an animal model already exists. It’s the rd16 mouse, a naturally occurring mouse with LCA, on which research has already begun. If tests show these mutations are amenable for gene therapy, it may not take too long for clinical trials to start, after the RPE65 trials!

For those forms of Leber's Congenital Amaurosis where photoreceptors have died, gene therapy will not be an option. However, other exciting research is going on that may benefit some of these patients. Stem cell transplantation is one option. Stem cells are cells that haven’t yet differentiated into specialized cells, and can be used to replace dead photoreceptors. Research is also been done on actual photoreceptor transplantation. Transplanted photoreceptors do survive in the eye, but connections to the remaining retina and optic nerve is still poor and more work needs to be done.
The retinal chip is also a promising, exciting object of research, close to commercialization. Many labs are working on it using different approaches. Dr. Mark Humayun presented his work, and reported excellent results. For now clinical trials of the chip are only recruiting patients with advanced retinitis pigmentosa, however in the future Dr. Humayun thinks such a device may benefit people with Leber's as well.

Dr. Stone gave a wonderful presentation on the Carver Lab’s LCA genetic screening program, how it operates and what its objectives are. I will report about this in a separate entry later on.

More genes causing retinitis pigmentosa are being found to cause LCA as well. The one discovered more recently is the IMPDH1 gene, which causes autosomal dominant RP and LCA. Dr. Stephen Daiger from the University of Texas explained that though LCA is commonly inherited in a recessive pattern, some rare cases of dominant LCA do exist and they should not be overlooked. RP genes may be good candidates to test in the search for the remaining LCA genes, and autosomal dominant mutations should be looked for as well. This strong connection between some forms of RP and some forms of LCA shows that these two retinal disorders are strictly related, so much that some subtypes of the two can be conceived more as a continuum rather than as two distinct diseases. The exciting news, as pointed out by researchers at the conference, is that discoveries made in one area of retinal research can be vital for progress in other areas.

Pharmaceutical Therapy for retinal diseases including LCA is also entering clinical trials. Dr. Gerald Chader explained that this would be a treatment, not a cure. Its aim will be to preserve photoreceptors which, even when not working properly, are still healthy and intact, as determined by a scan of the retina called an OCT. If photoreceptors are dead, drugs cannot bring them back to life; in this case, the retinal chip or cell transplantation will be an option.
Pharmaceutical Therapy has been shown to slow the photoreceptor cell degeneration in
animals with retinal degeneration, by prolonging their life. Drugs may be delivered into the eye by intraocular capsules that are time released.
Vitamin A (specific compounds) have also been shown to slow the course of the disease. Anit-oxidant supplements are also effective in slowing Age Related Macular
Degeneration.

To the specific question about restoring vision in an adult who was blind from birth, Dr. Irene Maumenee, of Johns Hopkins, replied that though nothing is certain about the brain’s ability to ”learn to see“, no attempt for treatment should be excluded solely on the basis of age. The brain has been proven to be highly plastic, and she believes that vision can be learned gradually, by training the brain, even in adults. Of course, the earlier a treatment is started, the better.

I think the news could not be better than this. This is an exciting time for research, and it’s great to be a part of it!

Take care

Fran

The newly identified LCA gene,CEP290

2006-07-16T12:18:00.000+02:00

Here’s the information I’ve been dying to have since Dr. Koenekoop was so kind to tell me that a new LCA gene had been found, and that I carried it!
Thanks to my wonderful friend Céline, who is a genetist and knows all about this stuff, I got ahold of this precious information which appears on the website of the American Journal of Human Genetics, due for publication in September.

I’m pasting the abstract of the article as it is. It’s highly technical but it all sounds so exciting!

Fran
The American Journal of Human Genetics Volume 79 September 2006

REPORT

Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis

den Hollander AI, Koenekoop RK, Yzer S, et al

Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for ~45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655° r G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far.

New gene official: it's recessive

2006-06-29T18:51:00.000+02:00

The new LCA gene is official! The researcher who has discovered it has given me permission to talk about it freely now, so I can mention his name. It is Dr. Robert Koenekoop from Montreal Children's Hospital in Canada. The name and function of the gene are going to be revealed in Cleveland at the LCA conference next July. However, we already know that it is recessive! This is great news for those with LCA caused by this gene who wish to have children, as with recessive patterns the affected person would have to have a partner with the same mutated gene, which is extremely rare. Also, as far as I know recessive mutations may be better targets for gene therapy, though it's probably a bit too soon to talk of therapy.

This is all very exciting!

Fran

Fantastic news: new LCA gene identified!

2006-06-06T21:19:00.000+02:00

A new gene causing LCA has been found!!! I can't tell you more, because I don't know more myself...But I hope I will in a few days.
Apparently, I carry a mutation in this gene, so for me it's double-excitement!

Just when we feel not much is going on in the field of LCA research, there we go!

I'll post asap with more news. Stay tuned!

Fran

Treatment still closer for LCA: another success

2006-05-26T00:33:00.000+02:00

Another breakthrough has been reached with animal gene therapy for LCA. This time the target was the Gucy2D mutation,which causes LCA1 - the first gene discovered to cause Leber’s, in 1997.
Embryos of chickens which would be born blind because of this mutation were injected the healthy gene, and after hatching they could see!

The authors point out that although gene therapy was delivered in utero, this doesn’t rule out that it may work on older patients too, once it is tried on humans.

Check the story at

or read the article at

Let’s hang in there!! Surely more great news to come in the near future.

Fran

Final conference schedule

2006-05-23T22:37:00.000+02:00

Hello,
this is supposed to be the final schedule of the scientific sessions of the 4th LCA conference. Judging from the presentations' titles, not a word should be missed!
I'll update this blog as soon as I can after the conference, maybe in realtime from Cleveland, with allthe exciting news that will come out. We cannot expect a miracle to happen in a few months, however with so much going on and considering the pace of research nowadays, we have good reason to hope that many of us who have lost their sight or who have never seen because of LCA will gain some vision one day not too far ahead.

Fran

FINAL CONFERENCE SCHEDULE

Saturday, July 29th 2006

Introduction
8:30-8:40 am Welcome and Opening Remarks
Dr. Hilel Lewis

Session 1: LCA Characteristics: Phenotypes and Genotypes

8:40-9:00 Clinical Characterization of LCA
Dr. Irene Maumenee

9:00-9:20 LCA Clinical Characterization: Phenotype- Genotype Relationships
Dr. Jill Hopkins

9:20-9:40 Genetic Testing in LCA
Dr. Edwin Stone

9:40-9:50 Q&A Session
Drs. Maumenee, Hopkins and Stone

Session 2: LCA Genes
9:50-10:10 LCA Gene Update
Dr. Steven Daiger

10:10-10:30 The Role of TULP1 in LCA
Dr. Stephanie Hagstrom

10:30-11:00 Break

11:00-11:20 Finding New LCA Genes
Dr. Robert Koenekoop

11:20-11:30 Q&A Session
Drs.Daiger, Hagstrom and Koenekoop

Session 3:
11:30-11:50 "Photoreceptor Development and Disease"
Dr. Connie Cepko

11:50-12:10 Gene Therapy
Dr. Jean Bennett

12:10-12:30 Stem Cell and Transplantation
Dr. Vas Sadda

12:30-12:40 Q&A Session
Drs. Cepko, Bennett and Sadda

12:40-1:30 Lunch

Session 4: LCA Therapies 2
1:30-1:50 Retinal Electronic Prostheses
Dr. Mark Humayun

1:50-2:10 Pharmaceutical Therapy
Dr. Gerald Chader

2:10-2:30 Potential for Retinoid Treatment in LCA
Dr. Krzysztof Palczewski

2:30-2:40 Q&A Session
Drs.Humayun, Chader and Palczewski

2:40-3:00 Break

Session 5 Summary and Conclusions

3:00-3:30 The Commercial Pathway to LCA Treatments
Dr. Eugene de Juan

3:30-4:00 Towards Treatments and Cures for LCA
Dr. Elias Traboulsi

4:00:4:30 General Questions and Answer Session

Per gli italiani: il 5 per mille alla ricerca sulla LCA!

2006-04-08T12:48:00.000+02:00

Riporto il testo della email che ho appena ricevuto dall'Associazione Italiana LCA (IALCA). Grazie alla Finanziaria 2006 ora è possibile donare il nostro 5 per mille delle imposte alla ricerca sulla LCA! Molto interessante.

Ciao

Francesca

Il tuo 5 per mille a sostegno della IALCA – ONLUS

La Legge finanziaria per il 2006 (Legge 23 dicembre 2005, n. 266) ha previsto, a titolo sperimentale, l'opportunità per il contribuente di sostenere la
ricerca e il volontariato destinando il 5 per mille dell'IRPEF dovuto all'erario similmente a quanto già previsto per l'8 per mille.

Le attività che possono essere sostenute sono quelle del volontariato, della ricerca scientifica, sanitaria e universitaria e delle attività sociali attivate
dal Comune di residenza del contribuente.

Il concetto è abbastanza rivoluzionario poiché il 5 per mille permette al cittadino di indirizzare una quota dell'imposta dovuta allo Stato trasferendo
quote di potere e di responsabilità dallo Stato alla società anzi, ai cittadini stessi e alle loro organizzazioni.

La scelta è valida per tutti i modelli di dichiarazione: UNICO persone fisiche 2006, Modello Integrativo CUD 2006, Modello 730-1bis redditi 2005.

In sede di compilazione della dichiarazione dei redditi, il contribuente deve apporre la propria firma a fianco dell'opzione prescelta: nel caso delle
Onlus, (Organizzazioni non Lucrative di Utilità Sociale) l'opzione è la casella "a".

-
nella medesima casella scrivere il codice fiscale della Ass.It.Amaurosi Congenita di Leber - IALCA 96036310181

Se non viene precisato il codice fiscale la vostra offerta sarà versata nel calderone generale delle Onlus.

E’ molto importante fare uso del passaparola, perché molte persone, familiari, parenti ed amici non sono a conoscenza di questa opportunità. Bisogna convincerli
ad assegnare il loro 5 per mille alla “ Associazione Italiana Amaurosi Congenita di Leber – IALCA - ONLUS” per aiutare concretamente la ricerca scientifica,
genetica e clinica di questa invalidante e rara malattia.

Contiamo su di voi ! e vi ringraziamo fin d’ora per il vostro aiuto
Fiammetta Boni Longo
Presidente IALCA
Email: amaurosicongleber@libero.it

Tentative Schedule for LCA conference 2006

2006-03-25T15:01:00.000+01:00

The LCA conference is drawing near! I’m glad to be able to post the tentative schedule. Thanks to Amber, Betsy and everyone at the Foundation for Retinal Research for their hard work!

If you need more info on the conference, please check the FRR site or drop me an email and I’ll be happy to help.

Fran

TENTATIVE CONFERENCE SCHEDULE

Thursday, July 27th and Friday, July 28th
§ Medical exams (by appointment only) at Cole Eye Institute

Friday, July 28th, 2006
5:00 – 7:00 pm
§ Pre-conference check-in
§ Evening activity

Saturday, July 29th 2006
7:30 – 8:30 am
§ Continental Breakfast & Registration
7:45 – 8:15 am
§ Child Care check-in at the Cleveland Sight Center
8:30 am – 4:45 pm
§ Medical research presentations
§ Lunch
§ Breakout sessions

Saturday Family Dinner with special key note speaker Kevin O’Conner followed by games and family fun.

Sunday, July 30th 2006
7:30 – 8:30 am
§ Continental Breakfast
7:45 – 8:15 am
§ Child Care check-in at the Cleveland Sight Center
8:30 am – 4:45 pm
§ Breakout sessions
§ Lunch
§ Breakout sessions

Monday, July 31st 2006
§

Conference Site: InterContinental
CLEVELAND
9801 CARNEGIE AVENUE
CLEVELAND, OH 44106
UNITED STATES
Tel: 1-216-7074100
Fax: 1-216-7074101
Email: cleveland@interconti.com
Check-In Time: 3:00 PM
Check-Out Time: 12:00 PM

Child Care: Cleveland Sight Center
University Circle
1909 East 101st Street
PO Box 1988
Cleveland, OH 44106-8696
Phone: (216) 791-8118
Fax: (216) 791-1101

Medical Exams: Cole Eye Institute
The Cleveland Clinic Foundation
9500 Euclid Avenue, Mail Code i-20
Cleveland, Ohio 44195
216/444-2020 or 800-223-2273 ext. 42020
Hotel: InterContinental
CLEVELAND
9801 CARNEGIE AVENUE
CLEVELAND, OH 44106
UNITED STATES
Tel: 1-216-7074100
Fax: 1-216-7074101
Email: cleveland@interconti.com

SATURDAY, July 29th , 2006
Scientific Program

7:30 – 8:30 Conference Check-In

8:30 – 8:40 David & Betsy Brint Welcome and Opening of 4th LCA Conference

8:40 – 8:50 Eugene de Juan Welcome to the Cole Eye Institute

8:50 – 9:10 Khaled Tawansy Eye anatomy and retinal degenerations

9:10 – 9:40 Irene Maumenee Clinical features of LCA

9:40 – 10:10 TBA Introduction to retinal genetics

10:10 – 10:20 Break

10:20 – 10:50 TBA Overview of LCA genetics

10:50 – 11:20 Irene Maumenee Latest discoveries in LCA gene research

11:20 – 11:50 TBA Future directions in LCA gene research

11:50 – 12:30 Panel Discussion Questions & Answers

12:30 – 1:30 Lunch

1:30 – 2:00 Gerald Chader Overview of Research in Retinal Degeneration

2:00 – 2:30 Jean Bennett Gene therapy for LCA

2:30 – 3:00 Eugene de Juan Drug delivery approaches for treating retinal degenerations

3:00 – 3:30 Vas Sadda Retinal transplantation and stem cells

3:30 – 4:00 Mark Humayun Retinal prosthesis

4:00 – 4:45 Panel Discussion Questions & Answers

4:45 Adjourn for the day

Saturday Family Dinner with special key note speaker Kevin O’Conner followed by games and family fun.

SUNDAY, July 30th 2006

Break-Out Sessions and Discussion Groups

8:30 – 9:30 First Session

9:45 – 10:45 Second Session

11:00 – 12:00 Third Session

12:15 – 1:30 Lunch

1:45 – 2:45 Fourth Session

3:00 – 4:00 Fifth Session

The specific schedule and speakers for Sunday have not been finalized. Discussion groups will be divided up by age groups and topics. Break out session topics and presentations will include, but are not limited to:

Technology
Braille Literacy
Orientation and Mobility
Daily Living Skills
Sports and Recreation
Early Intervention
Games and Toys
Vocational Opportunities
Braille Music
IEP Training
NAPVI (National Association of Parents of Children who are
Visually Impaired)
Support Systems

MONDAY, July 31st, 2006

Family Activity

Rock n Roll Hall of Fame and Great Lakes Science Center

Statement by Dr. Bennett on upcoming clinical trials

2005-12-23T16:36:00.000+01:00

It is real! It is really going to happen. Human clinical trials on gene therapy for LCA caused by mutations in the RPE65 gene are scheduled to begin next year! Two trials are planned, one enrolling adults and one for children. What follows is a statement by Dr. Jean Bennett, a leading researcher in LCA gene therapy, which was sent directly to the Foundation for Retinal Research. If you have any question just email them to me and, if necessary, I’ll forward them to FRR.

Enjoy!

Fran

On Tuesday December 13, 2005, the Recombinant DNA Advisory Committee (the RAC) at the National Institutes of Health (NIH) unanimously approved a pediatric clinical trial for Leber congenital amaurosis (LCA). This approval was a landmark event because it endorsed the idea that the risk/benefit ratio of a clinical trial in a pediatric population with this disease is acceptable. Traditionally, investigators have avoided studies in pediatric subjects until safety had been established in studies of adults.
The Principal Investigator of this trial, Dr. Albert Maguire (Scheie Eye Institute, University of Pennsylvania) explained to the RAC that the first human studies in this trial, which will involve 8-18 year old subjects with mutations in the RPE65 gene, will emphasize safety of the treatment but that there is a potential for benefit with respect to visual function. He explained that, due to characteristics of the disease and of the biology of visual development, there is a higher likelihood of restoration of vision in a pediatric population than in an adult population. If the treatment is shown to be safe in these phase I studies and additional regulatory approvals are given, younger subjects could be enrolled. At the RAC meeting, Dr. Jean Bennett, scientific director of the study and professor at the F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, showed data demonstrating rescue of vision in dogs and mice with this form of the disease with minimal evidence of toxicity. The investigators hope that the studies approved by the RAC will ultimately lead to a similar effect in children. This study is sponsored by the Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia. The team is completing additional safety studies relating to this clinical trial and seeking additional funds to support the studies, and anticipates that the first subjects may be enrolled in late 2006.
This pediatric clinical trial will be complemented by results from an adult clinical trial for the same disease (PI, Dr. Samuel Jacobson, University of Pennsylvania). Updates on the timelines of these two trials will be available from the Foundation for Retinal Research.

--

Jean Bennett, M.D., Ph.D.
Ophthalmology; Cell and Developmental Biology
University of Pennsylvania
Philadelphia, PA 19104

Therapy works in a mouse model of LCA

2005-11-03T10:55:00.000+01:00

A work has just been published on PLoS Medicine, announcing the incredible results obtained with intraocular gene therapy plus oral pharmacological treatment on mice affected with LCA caused by mutations in the Lrat gene.

The authors sound very hopeful about future therapy in humans, and they do not rule out the possibility of restoring sight in adults, at least in some forms of LCA.

The full text is available online free of charge at
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020333

Do check it out! It’s a bit technical but the main messages sure come through. This is all very exciting.

Take care and stay tuned for more!

LCA conference 2006: registration begins

2005-09-28T12:14:00.000+02:00

It is now possible to register for the 2006 LCA conference held in Cleveland Ohio. You can find the forms and all there is to know on the Foundation for Retinal Research web site at

Though it's almost 1 full year ahead it's wise to register quickly as space is limited.

Fran

Restoration of useful vision: Dr. Edwin Stone's view

2005-08-20T18:46:00.000+02:00

A few days back I had emailed Dr. Edwin Stone from the University of Iowa to congratulate him on the wonderful presentation he gave (see previous post). I wasn’t expecting any reply as I asked no question. Instead he wrote back, even thanking me for taking the time to let him know! A beautiful correspondence followed. He gave me permission to publish his email to me concerning the possibility of sight restoration to adults born with no vision, and on the usefulness of even very poor sight.

Here it is below. I’m sure it will be inspiring to many, not just because it’s so optimistic and positive, but above all for his sensitivity and kindness.

Fran
Dear Francesca,
Thanks for your most recent message.

Here is my short answer: I DO believe that some people who have been blind since birth will eventually be able to gain some useful vision from some type of surgical or medical intervention.

Why do I believe this?

1) Briard dogs with Leber's congenital amaurosis (LCA) who are old enough to be visually mature (that is, dogs whose cortical wiring is already complete) are able to regain very useful vision following injection of a viral vector with a functional RPE65 gene under the retina.

2) A 6 year old patient of mine with LCA who can see only hand motions at 1 foot is able to distinguish the border between her yard and her driveway when she is riding her bike. She can also distinguish the edges of doors and curbs bordering roads. She and her parents feel that all of these things help her to function in her daily activities -- that is, that her hand motions vision is "useful" to her.

3) Most patients with LCA have very healthy looking optic nerves even when their retinas look terrible. This suggests that if some new photoreceptive cells can be put into the retina (via some type of stem cell therapy) OR if the remaining ganglion cells can be stimulated (by some type of electrical retinal prosthesis) that the pathways from the eye to the brain are still healthy enough to carry useful information.

4) In 1996, we could identify the disease causing mutations in ZERO percent of patients with LCA. In 2005, we can identify disease causing mutations in over 50% of patients!

5) in 1984 (prior to the invention of the polymerase chain reaction) we could analyze a single gene for mutations in perhaps 5 to 10 people per year. Today, our laboratory can study a single disease causing region of a gene in 2500 people in a single day. This was made possible when a scientist named Kary Mullis figured out how a little microbe that lives in hot springs copies its DNA and then harnessed that microbe's DNA synthesizing machinery to do our bidding.

6) A tiny zebrafish egg with no visible structure to it can develop into an animal with a retina that is very similar in structure to a human retina in just 72 hours. All of the information needed to make a retina is in that little egg. I believe scientists will be able to learn some of the critical steps in this process and use that knowledge to convert stem cells into functional retinal cells for humans.

The points that I am trying to make are: vision doesn't have to be very good for it to be useful, restoration of vision in large visually mature animals who are "blind from birth" has already occurred, and the overall pace of research progress in the past 20 years is nothing short of breathtaking.

So why do some people say that people who are blind from birth will not be able to have their vision restored? Well, for one thing, all patients are different and a treatment that works for one person (or for a dog) may not work at all for another person. Thus, one cannot promise a given patient that they will recover some vision and they certainly cannot promise them that they will recover it by a certain date. (For example, in 1982, I spent 14 months analyzing 4000 base pairs of DNA from a single individual. I would not have been able to predict that the polymerase chain reaction was going to be developed just three years later and that that would allow us to analyze 4000 base pairs of DNA in 20 people in a single day).

I must say that I myself want to avoid suggesting that cures for retinal degenerative diseases are "just around the corner" because I honestly believe that there is still quite a bit of work to be done to develop useful treatments for most of these diseases. However, I also believe that these treatments will be developed and that in my professional lifetime some people who are born with a non-functioning retina will receive a treatment that will allow them to have ambulatory vision or better. To put it another way, I have hope that this will occur. My favorite definition of the word "hope" is "a desire accompanied by confident expectation". One needs hope in this business whether one is the doctor or the patient and I honestly think that we have lots of realistic basis these days for "confident expectation".

So, that was a long answer to a short but very good question. I appreciate your asking it.

Regards,

Ed

Next LCA conference scheduled for July 2006!

2005-08-08T22:24:00.000+02:00

The Foundation for Retinal Research (FRR) will be holding their fourth Bi Annual Leber’s Congenital Amaurosis Conference on July 26-31, 2006. The event will take place in Cleveland, Ohio, USA, at the Cole Eye Institute along with the Cleveland Clinic and the Cleveland Sight Center.

This is a wonderful opportunity for families and patients to bring your list of questions and speak directly to some of the best researchers and doctors in the field, all committed to scientific research and working hard to find cures and treatments for people with Retinal diseases like LCA.

Before the actual conference begins, the Cole Eye Institute will give patients the opportunity to undergo medical exams, ERGs, and to give blood samples for retinal research.

Here are a few rough details for scheduling purposes:
Wednesday July 26 - Friday July 28: Eye exams. The doctors from Doheny and the Cole Eye Institute will join forces to see as many patients as possible. Blood samples for genetic testing will also be collected.
Friday night July 28: Conference registration and opening night party.
Saturday July 29 - Sunday July 30: Scientific presentation sessions from the leading researchers and doctors working on LCA, Daily Living Skills Presentations, Break-Out Sessions, etc.
Monday July 31: Family Outing. Exact location TBD.

For any questions please contact FRR at
work2see@aol.com

Very interesting presentation by Dr. Stone

2005-08-07T23:33:00.000+02:00

Dr. Edwin Stone, researcher at the University of Iowa, just gave a wonderful presentation on April 8th at the New England Ophthalmological Society regarding LCA, focusing on genetic testing and the promising prospects of gene therapy.
It's a very optimistic and at the same time realistic talk, very clear also for the layman. Among other things he seems to suggest that therapy may work in adults with just light perception since birth!

You can hear the presentation by logging on to

and clicking on "view the presentation".
Though the site says the clip will also work with Windows Media, I was only able to play it with Real Player.

Listen to it, it's great!

RP gene found to cause LCA!

2005-07-14T18:10:00.000+02:00

Researchers just reported at the ARVO (Association for Research in Vision and Ophthalmology) meeting last June that mutations in IMPDH1 cause LCA.
Mutations in this gene had already shown to be responsible for a form of dominant Retinitis Pigmentosa called RP10.

Scientists believe this type of LCA may be dominant, though this still needs to be confirmed.

I'll post more about this new gene as soon as I get more information. It's so exciting to see that research is going forward, and probably even not as slowly as we might perceive it to go...!

Fran

Gene therapy clinical trials will begin this fall!

2005-02-24T15:03:00.000+01:00

It's official. According to an article just published on the Foundation Fighting Blindness website, phase I gene therapy clinical trials for the type of LCA caused by RPE65 are scheduled to begin in fall 2005. This is wonderful news. You can read about this and more here

And stay tuned for more!

Incredible news from the world of electronics

2005-02-16T23:48:00.000+01:00

A member of the LCA mailing list has just shared the most exciting article on the different retinal chips being developed. Their widespread application seems to be only a few years away, and with some features that I only thought possible in sci-fi movies! But no, this is science. I recommend everyone read it at
http://www.eetimes.com/showArticle.jhtml?articleID=51200440

And stick around this site for much more!

Fran

Retinal implant seems to work! New trials coming up

2005-02-11T18:54:00.000+01:00

Optobionics first began human clinical trials in 2000, to test the safety of its retinal implant called the Artificial Silicon retina ASR. Now new human trials are scheduled to begin, this time with the aim to verify the implant’s effectiveness!

All patients enrolled in the trial who received the ASR reported vision improvement. Patients enrolled in the upcoming trials will be followed for at least 2 years. This is really exciting news. For the first time we learn that the Optobionics implant is really capable of improving sight. Of course we cannot know if it will work on all patients with LCA, but this is very encouraging. You can read more at http://www.betterhumans.com/News/news.aspx?articleID=2005-02-09-2
or visit the Optobionics website

Read the abstract on previous clinical trial

From the Retina Transplant Newsletter by Dr. Peter Gouras

2004-10-29T21:03:00.000+02:00

Besides being the most wonderful person, Dr. Peter Gouras is a leading researcher involved with retinal disease and gene therapy, at the University of Columbia, New York. Currently he’s mostly involved with Stargardt’s disease but his work also has implications for LCA. Here are extracts from his latest newsletter. I thank Dr. Gouras for his work, his enthusiasm, and his kindness.

Fran

Newsletter

Volume 12 Number 1 November, 2004

By Peter Gouras, M.D.
mailto:pg10@columbia.edu

Gene Therapy

This holds great promise for the treatment of retinal disease. The first commercially available gene therapy drug is close to approval by the Food and Drug Administration. The drug, Advexin, will treat cancer by correcting a p53 gene defect in solid tumors. Other companies are in trials to clear gene therapy for retinal disease. Advance Vision Therapies in Rockville, MD has developed vectors to deliver genes to the retina to stop CNV or to prevent photoreceptors from degenerating in AMD or Retinitis Pigmentosa. The University of Pennsylvania has been awarded $10 million from NIH to develop a viral vector to cure a childhood form of retinal degeneration, Leber's Congenital Amaurosis. We at Columbia are working on gene therapy for autosomal recessive Stargardt dystrophy, a not uncommon form of macular degeneration in children.

Gene therapy began in the 1990s but had several setbacks. The death of the teenager Jesse Gelsinger at the University of Pennsylvania from an immune response to the viral vector carrying therapeutic gene was a tragedy. Then an attempt by the French to cure severe combined immunodeficiency, "bubble boy disease" caused cancer in two of the eleven treated infants, prompting the FDA to stop 27 gene therapy trials. In May, Avigen also halted gene therapy for hemophilia because of safety issues. The U.S. Hemophilia Foundation regrets this and wants to redouble its efforts to promote gene therapy research. From a peak of 114 gene therapy trials in 1999 research has been reduced to 74 trials in 2003. But gene therapy has regained impetus. The retina is a good place for gene therapy. Threats of cancer and/or immune complications are less than when the entire body is treated and now methods are developing to eliminate such complications. Watch for big gains in this field soon.

Blood Samples for Genotyping

As gene therapy advances it will become important for patients with retinal disease to know the genetic nature of their disorder. Many are due to a single gene defect making them ideal for correction by gene therapy. Others such as AMD are due to multiple and still unknown gene deficiencies making gene therapy unrealistic at present, at least as means of correcting the basic problem. But how does one determine the genetic nature of his or her retinal disorder? At present there is no screening center that will do this for all possible disorders even at a cost. It would be wonderful if this could be developed but it is still too cost intensive and therefore unprofitable for private industry. Perhaps, the NIH should create a genetic diagnosis center or out source this project to several major university centers currently doing this. Eventually such services should become available to ophthalmologists through out the US so that precise diagnoses become available for all genetic disorders of the eye. Now there is no urgency but as gene therapy evolves such services will be needed. New York State has instituted a gene typing laboratory to check all infants born in the state for AIDS, cystic fibrosis and several other rare genetic diseases. This will be expanded in a few years to include 44 genetic defects present in the newborn. This is a great step in the right direction and should eventually include all genetic defects.

Restoring Vision

This is the dream of many. The hero of functional restoration of the central nervous system, Christopher Reeves, recently succumbed to his malady spinal cord injury. He argued for stem cell research and neural cell transplantation in an effort that should not be forgotten. He was right. Many experiments need to be done, all of which need more funding.

Embryonic stem cells are undifferentiated cells capable of becoming neurons or photoreceptors. They can be obtained by somatic cloning (ethically very controversial), or from therapeutic abortion (equally controversial) or from a person's bone marrow (acceptable). Adult stem cells may also be effective and can be obtained from other parts of the body including the eye. The current presidential administration has handicapped stem cell research putting American researchers and science as a whole at a disadvantage. We must lobby support for stem cell research and its corollary neural cell transplantation and reconstruction of the central nervous system.

The fovea is a wonderful target for such research because it involves only one-way transmission. Photoreceptors respond to light; they only need to communicate with second order neurons, which are within fractions of a millimeter away. What an exciting event when we can restore lost neurons and reconnect them to their correct targets! It will come just as Christopher predicted. It will be interesting to see whether transplantation of photoreceptors is a better way to restore vision than the placing of an electronic microchip in the retina.

The Retinal Chip

This still has a long way to go but the scientists involved are all determined to move ahead with this difficult but intriguing device because an analogous device on the auditory nerve has been so successful in greatly helping deaf children. The University of California group is organizing a clinical trial of their current device which is fixed to the surface of the retina. The results of this study will not be available for several years but it is an important step in the right direction.

Tax-deductible contributions are very much needed and can be made to the Foundation for Retinal Research, Inc. The IRS tax identification number is 13-3771936 and the New York State registration number is 63469. Send any donations to Peter Gouras M.D., Columbia-Presbyterian Medical Center, 635 West 165th Street, Box 76, New York City, New York 10032

DOE labs, universities and second sight partner to speed development of 'artificial retina'

2004-10-15T21:01:00.000+02:00

Contact: Jeff Sherwood
jeff.sherwood@hq.doe.gov
202-586-5806
DOE/U.S. Department of Energy

DOE labs, universities and second sight partner to speed development of 'artificial retina'

Restoring sight through science
CHICAGO, IL – In an effort to speed the design and development of an artificial retina that could potentially help millions of people blinded by retinal diseases, Secretary of Energy Spencer Abraham announced today that five Department of Energy (DOE) national laboratories, a private company and three universities have signed agreements to form a research partnership.

The goal of the agreements signed today is to advance the science, technology and clinical success of the field of artificial sight using the facilities and resources of DOE's national laboratories.

At today's announcement in Chicago, the first patient to receive a prototype implant in 2002 described what it was like being able to "see" large letters and to differentiate between a cup, a plate and a knife after being blind for over 50 years. To date, six volunteers have received implants of a micro-electronic device that rests on the surface of the retina to perform the function of normal photoreceptive cells. The artificial retina technology was featured at the department's "What's Next Expo," an event designed to showcase the newest, most innovative, cutting-edge scientific and technological advances to interest young people in pursuing careers in math and science.

"The Department of Energy has led the way to many scientific breakthroughs, especially when several scientific disciplines combined to make a whole greater than the sum of the parts," Secretary Abraham said. "This project is one such example where biology, physics, and engineering have joined forces to deliver a capability that will enable blind people to see. This agreement between the DOE laboratories and the private sector will facilitate transfer of many aspects of DOE technology to a clinical device that has the potential of restoring sight to millions of blind individuals."

The agreements allow Second Sight Medical Products Inc. based in Sylmar, Calif., to obtain a limited exclusive license for inventions developed during the artificial retina project. Under the research agreements, the institutions will jointly share intellectual property rights and royalties from their research. This will speed progress by freeing the researchers to share details of their work with their collaborators.

The artificial retina could help those blinded by age-related macular degeneration or retinitis pigmentosa where neural wiring from the eye to brain is intact, but the eyes lack photoreceptor activity. The artificial retina is a device that captures visual signals and sends them to the brain in the form of electrical impulses. The device is a miniature disc that contains an electrode array that can be implanted in the back of the eye to replace a damaged retina. Visual signals are captured by a small video camera in the eyeglasses of the blind person and processed through a microcomputer worn on a belt. The signals are transmitted to the electrode array in the eye. The array stimulates optical nerves, which then carry a signal to the brain. The first prototype implants contain 16 electrodes. The next prototype, with 50-100 electrodes, is in preclinical trials. The project's "next generation" device would have 1,000 electrodes and hopefully would allow the user to see images.

The Department of Energy-supported project is a collaboration of DOE national laboratories, universities and the private sector:

Oak Ridge National Laboratory and the University of Southern California Doheny Eye Institute are leading the multi-laboratory effort. Oak Ridge's research includes developing better electrodes and fabrication techniques and studying the long-term stability of the device once it is implanted.

Argonne National Laboratory scientists, in collaboration with Second Sight, are using their patented ultrananocrystalline diamond technology to make the implant biocompatible with the surrounding ocular tissue.

Lawrence Livermore National Laboratory is developing a thin, flexible implant that can conform to the curved shape of the retina.

A Los Alamos National Laboratory team is developing advanced optical imaging techniques. They are providing a better understanding of how the prosthesis works, by mapping the interaction between the brain and retina.

Sandia National Laboratories researchers are developing advanced electrodes using MEMS (micro-electro-mechanical systems) research.

The University of Southern California Doheny Eye Institute provides medical direction of the project and performs clinical testing of the implants.

North Carolina State University is performing electrical and thermal modeling of the device to help determine how much energy can be used to stimulate the remaining non-diseased cells.

University of California, Santa Cruz work includes wireless communication technology to provide the link between the camera and the implant.

Second Sight created the prototype device that is currently in testing. Second Sight will integrate DOE technology into product designs that will eventually move on to clinical trials.

Using the unique resources of the DOE national laboratories in materials sciences, microfabrication, microelectrode construction, photochemistry and computer modeling, the project's goal is to construct the device, capable of restoring vision, with materials that will last for the lifetime of a blind person. Although images will initially be captured by a camera housed in an eyeglass frame, researchers hope eventually to develop a completely implanted system for this purpose. DOE's effort is focused on developing high-grade microelectrodes and testing their long term biological effects, developing electrode and platform materials that are pliable and will last a lifetime within the eye, constructing a completely wireless device for clinical use and performing the computational modeling of long-term retinal stimulation.

The Energy Department's Office of Science plans to fund the artificial retina project at $20 million over the next three years. The department funds the project as part of its medical applications technology program. DOE and its predecessor agencies have been in the forefront of imaging sciences including clinical imaging in nuclear medicine and imaging atoms at synchrotron light sources. The National Institutes of Health and the National Science Foundationare also supporting the project.

###

Additional information on the artificial retina project is available at
www.science.doe.govand from the participating institutions' press offices:

Argonne National Lab, Catherine Foster, 630-252-5580
Lawrence Livermore National Lab, Anne Stark, 925-422-9799
Los Alamos National Lab, Todd Hanson, 505-665-2085
North Carolina State University, Mick Kulikowski, 919-515-3470
Oak Ridge National Lab, Ron Walli, 865-576-0226
Sandia National Laboratories, Neal Singer, 505-845-7078
Second Sight, Robert Greenberg, 818-833-5000
University of California, Santa Cruz, Tim Stephens, 831-459-4352
University of Southern California, Jon Weiner, 323-442-2830

Update from FFB VISIONS 2004 Conference: hope is becoming reality

2004-08-26T19:00:00.000+02:00

My friend Rachel has allowed me to post a very exciting and clear account of the Foundation Fighting Blindness VISIONS 2004 conference she just posted on the LCA list. Her report made my day!

Thanks Rachel for sharing.

Fran

Hello everyone,

My husband and I were able to attend the Foundation Fighting Blindness VISIONS 2004 conference last weekend in Chicago. I just thought I would share a little with the group on what was discussed over the 3 days.

Overall the conference was very good. Everyone was so positive and the information being shared was very hopeful. The days were filled with various sessions, some large and some on a smaller scale. They had special
"The Dr. Is In" sessions available for people to attend. These sessions were intended to be for smaller groups and had specific topics like Genetic Counseling, RP, Stargardt & Rare Diseases, & Strategies for Children with Low Vision, etc. Now they didn't have a specific group for LCA, so we chose to attend the "other rare disease" when applicable.

I will admit that the general sessions were biased to RP and Macular Degeneration. However, when they did talk about LCA, it was the most inspiring. They have come so far with the gene therapy. It appears that Phase I clinical trials are still on track to start some time next year. They really expect things to take off after that. I can't even begin to describe the excitement in energy about this that the speakers displayed. This is almost such a reality for us. We are lucky to be part of such an exciting time on the medical breakthrough to treat vision loss.

There are two things I found interesting. One was how so many of these diseases and syndromes overlapped. LCA was not very well represented in the audience. I heard of some diseases for the first time. There were a lot of people representing children with Usher's syndrome and Stargardt's disease. They are working on gene therapy for these diseases too. The FFB said that 60% of their funding/research is for RP, and 11% for LCA (the second largest). And they reminded us that LCA is a subgroup of RP. So that's 71% of their effort is going towards us. The second thing that I found
interesting is about the timeline for administering gene therapy. In LA at the LCA conference, it seemed like the scientist were telling us that the earlier the treatment (age) the better the results. At least for us, it left us wondering if we would miss our opportunity for our young son. But here, they said that they expect that gene therapy as treatment to restore vision could be used to treat patients even later in life.

The doctors did stress the importance of finding out about the defective gene the patient carries. It's important to know first whether it is recessive, dominant, or x-linked. Then, if you can find out which gene mutation has occurred, the better chances for successful gene therapy. For now, there is no "silver bullet", as the doctors put it, that would cover any/all genes. Plus, I think having that gene identified gives you the final piece of mind that your diagnosis was correct.

All in all, my final thoughts to share about this are: It's coming. There
was never any talk about 'If", everything was WHEN.

If anyone has questions about the conference, please feel free to
ask.

Thanks,

Rachel Miller
(Griffin, 2, LCA, low vision)

If you have any questions about the conference, email us

New LCA gene identified!

2004-08-24T22:54:00.000+02:00

Researchers from Paris have just announced the discovery of another gene causing Leber’s Congenital Amaurosis!!

It is the photoreceptor-specific RDH12 gene. All patients carrying RDH12 mutations seem to exhibit a severe, progressive rod-cone dystrophy with severe macular atrophy.

Another exciting step forward toward future treatments!

Click here for the abstract of the article published this month

Cure for Leber's Congenital Amaurosis: genetic testing is essential

2004-08-16T13:54:00.000+02:00

A cure for Leber’s congenital amaurosis LCA is becoming more and more realistic, and may not be too far ahead, at least for some forms of the disease. Since LCA is a collective name for very different retinal conditions, treatments will probably need to be disease-type specific. The type of LCA is determined by the genetic mutation the patient carries. It’s therefore important that THE blood of the patients is analyzed in order to find out which gene is defective.

If you have been diagnosed with LCA, you should consider giving a blood sample to labs specialized in genetic testing for two reasons:

1. If you still haven't been tested for the six LCA genes known so far, the test will reveal if you do carry one of them.

2. If the six LCA genes are ruled out in your case, your blood will be further studied in order to determine the gene responsible for your disorder, which will benefit both you and the entire LCA community.

SPECIALIZED LABS

LCA is a rare disorder, and only specialized labs so far are concerned with it. The number is growing and they are scattered all over the world. What follows is a link of researchers you may want to contact to have more information. Some labs may only perform genetic testing of the known genes, while others are also carrying out research. Also, some may require a fee, while others may offer it for free. Please contact them and ask, or email me and I will see if I can help. Please note that this list is not comprehensive and there may be many other labs involved with LCA that I don’t know of. If you know of a lab that I haven’t mentioned, or if you find any broken links on this page, please contact me.

Thanks!

Francesca – Italy, LCA patient

Dr. Irene Maumenee
Johns Hopkins Center for Hereditary Eye Disease, Baltimora, Maryland, USA
jhched@jhmi.edu

Dr. Richard A. Lewis
Cullen Eye Institute, Houston, Texas, USA
rlewis@bcm.tmc.edu

Dr. Josseline Kaplan
Hopital des Enfants Malades, Paris, France
kaplan@necker.fr

Dr. Samuel Jacobson
Foundation's Research Center at the Scheie Eye Institute of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
jacobsos@mail.med.upenn.edu

Dr. Markus Preising
Department of Paediatric Ophthalmology, Strabismology, and Ophthalmogenetics, University of Regensburg, Germany
markus.preising@klinik.uni-regensburg.de
(fee required)

Dr. Rando Allikmets
Department of Ophthalmology, Columbia University, New York, USA
rla22@columbia.edu

Cole Eye Institute - Research Center
The Cleveland Clinic Foundation, Ohio, USA
(currently enrolling patients with retinal disorders for genetic research)

Dr. Edwin StoneUniversity of Iowa Health Care
Carver Laboratory for Molecular Diagnosis
Iowa City, Iowa, USA
(will screen for the known LCA genes and for candidate genes. The screening for known genes can be requested for free on a research basis, or for a fee, depending on the speed patients wish to receive the results.)

Dr. Robert KoenekoopRobert.koenekoop@muhc.mcgill.ca

Dr. Robert Henderson
Institute of Ophthalmology, ept Molecular Genetics, 11-43 Bath Street - London UK
smgxrhh@ucl.ac.uk

Share with LCA patients and their families

2004-08-11T21:45:00.000+02:00

If you’d like to meet LCA adults, or parents of children with LCA, an email list has been created at yahoogroups, which now features more than 300 members. It can be a very helpful environment to learn more about the latest developments in research, to share experiences, and to ask and give advice on everything related to LCA and blindness.

To subscribe, simply send an email to
LCA-subscribe@yahoogroups.com

Once you’re a member, you can post to the group by sending an email to the address indicated in the welcome message you’ll receive, which will be read by all other members.

The group is unmoderated. Posts are in English but the list comprises people from every part of the world.

Ciao to everyone

Francesca – Italy

email me

Amaurosi Congenita di Leber in italiano

2004-08-11T21:29:00.000+02:00

Buongiorno a tutti! Sono Francesca, una ragazza italiana di 33 anni affetta dalla Amaurosi Congenita di Leber, LCA. Ho creato questo blog per diffondere e condividere informazioni utili su questa patologia. Tutte queste pagine sono in inglese – al fine di renderle accessibili al maggior numero possibile di visitatori – ma non esitate a contattarmi per email usando questo modulo e sarò felice di rispondervi in italiano.

In Italia esiste un’associazione no-profit che riunisce pazienti con LCA e le loro famiglie, denominata IALCA (Italian Association LCA), creata nel 1999 con sede a Pavia. La funzione dell’Associazione è quella di diffondere informazioni sempre aggiornate sulla patologia e di promuovere la ricerca, inviando campioni di sangue dei pazienti ai laboratori preposti e aiutando le famiglie a mantenere rapporti diretti con essi. Clicca qui per visualizzare il sito della IALCA, per contattarli, o per dare un contributo.

Un altro sito italiano interessante e informativo sulla LCA è quello dedicato a Matteo, un bambino fantastico e travolgente, affetto da LCA.

Cari saluti a tutti

Francesca - Parma

Help retinal research; simply enjoy reading!

2004-08-11T11:24:00.000+02:00

Hi friends,

Did you know that you can help support retinal research and get a great deal on digital audio entertainment? Joining AudibleListener® is a great way to help others while you do something wonderful for yourself. You'll get access to informative and entertaining audio programs, and the Foundation for Retinal Research will receive a generous donation from Audible.

Audible provides digital audio entertainment that lets you listen anywhere you go. Choose from best selling audiobooks, audio magazines, newspapers, radio programs, and more. Solve a mystery with James Patterson at the gym. Laugh with Al Franken on your way to work. Learn Spanish while you walk the dog. Download in minutes and listen in on your Audible Otis® MP3 player, Apple® iPod™, Palm OS handheld, Pocket PC, right on your computer, or on CDs you burn yourself.

Join AudibleListener and get two great audio programs of your choice each month for one low price. When you join, Audible will donate to the Foundation for Retinal Research $6 each month for the first 4 months of your subscription! And you’ll get a free gift! Choose a free month of The New York Times Audio Digest or a free Otis MP3 player!

Go to www.audible.com/fundraising/frr2004 and sign up today! Please make sure to sign up using the specified URL, and not from Audible’s homepage.

To learn more about the Foundation for Retinal Research, click here

If you have any questions concerning the Foundation, or about other ways you can support us, please contact us

Thanks for reading! Remember, LCA may be cured in the near future, and you can make a difference!

Francesca – Italy (33 year-old LCA patient)

Facts on Leber's Congenital Amaurosis

2004-08-10T16:30:00.000+02:00

Leber's Congenital Amaurosis (LCA) is a genetically inherited disorder which causes congenital blindness or very severe visual impairment. The genes causing LCA are many, each involving different physiological processes, but all concerning the retina's photoreceptors, or the retinal pigment epithelium. Vision in LCA ranges from total blindness to low vision. It is generally diagnosed in the first few months of life. Currently 6 genes responsible for LCA have been identified, and researchers think at least as many are there to be discovered.

In some forms of LCA, the retinas don't develop correctly; in others, the photoreceptors gradually degenerate; in other types the retina remains intact, photoreceptors are healthy but don't function properly (Koenekoop 2004).

THE FUTURE: LCA MAY BE TREATED!

LCA is the most severe form of congenital blindness, yet recent studies have demonstrated that it may be one of those conditions amenable for treatment. Since it usually only affects the outer layers of the person's retinas, and the rest of the visual pathway seems to remain intact, even in adult subjects, vision may be restored - at least in selected LCA patients.

Possible future treatments include:

1. GENE THERAPY: in simple terms - I'm not a doctor! - gene therapy aims at replacing a person's faulty gene with a healthy one. The genetic material is introduced into the body by means of a virus (a good virus), which once in the body starts to replicate and spreads the good genes to the target cells. In 2001, researchers at Cornell University restored vision in dogs affected by a form of LCA caused by a mutation in the RPE65 gene (Acland 2001). This proved that gene therapy does work for at least one form of LCA. Clinical trials on humans carrying the RPE65 mutation are planned for as early as 2005. If gene therapy proves successful it is very likely that it can be extended to patients carrying different LCA mutations. Click here to view a recent, very clear and comprehensive explanation of gene therapy and its prospects for LCA and other retinal diseases, by the Foundation Fighting Blindness.

2. RETINAL CELL TRANSPLANTATION: since LCA affects the photoreceptors of the retina (rods and cones, cells which transform light into visual impulses) or the retinal pigment epithelium (the outermost layer of the retina which is essential for photoreceptor nourishment and maintenance) usually leaving the rest of the visual pathway intact, vision may be restored by replacing the faulty cells with healthy ones, from healthy donors or stem cells. Various trials on animal models have shown that transplanted cells do survive indefinitely, and that to a certain extent they form synapses (they build a contact) with the rest of the retina. Researchers now have to find ways to improve synapses, which will allow the brain to receive clear information from the retina. This is challenging, but very thrilling, as such a procedure has the potential to restore vision to a blind eye affected by most retinal diseases.

3. PHARMACOLOGICAL THERAPY: for some types of LCA where the retinas remain intact and photoreceptors don't die - though they don't function properly - drugs may be developed which can slow or even reverse the problem. Currently, to my knowledge, researchers are trying to develop such a drug for LCA1 (LCA caused by mutations in the photoreceptor specific retinal guanylate cyclase gene GUCY2D), using a mouse model (Perrault 2003).

4. ARTIFICIAL RETINA: in many laboatories around the world, researchers have been working for years at the development of an artificial retina, or retinal chip, which will act as the person's lost or malfunctioning photoreceptors and turn light into visual impulses sent to the brain. Each lab is using a different technique: some implants work with solar energy, others require batteries and a camera linked to a pair of glasses. Some are positioned on top of the retina, others under the outer layer. Human trials have been going on for a few years, and though final results are not yet known, it has been established that the implants are safe and cause no damage to the patient. Projects currently underway include:

Artificial Silicon Retina

The Boston Retinal Implant Project

Artificial Retina Project

IMPORTANT

Like I said, I'm not a doctor and the information provided may not be 100% scientifically accurate. I am a 33 year-old patient with LCA, and I constantly keep myself up-to-date with research, anxiously waiting for breakthroughs.

If you have any question, need information, or would like me to post something specific on this site, please email me using the contact link on this page and I'll get back to you asap. If you would like to post your comments or experiences with LCA on this site, just drop me an email and I'll be more than glad to consider it.

I thank my wonderful friend, Mir Atta, for helping me with this site and with everything else...

Talk to you soon with my next post!

Francesca - Italy

Contact