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

(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