Scientists studying blindness are attracted to the transformative potential of gene therapy because it can profoundly impact the lives of people living with vision loss.
The eye is an ideal organ for gene replacement therapy because it is 1) accessible, 2) less likely to reject the new gene, 3) small in size, 4) isolated from the rest of the body, and 5) has its own ‘control group’, in that you can treat one eye and not the other for the purpose of observation. For these reasons, many researchers are pioneering gene therapies for different genetic forms of blindness.
Dr. Robert Molday’s research, funded by the Foundation Fighting Blindness, is driving retinal gene therapy forward. A leader in the field of gene therapy, Dr. Molday has been involved since early in its development. Initial gene therapy studies focused on replacing ‘small genes’ that could fit inside the most commonly used viral vectors, such as those used in the RPE65 trial directed at Leber congenital amaurosis (LCA2). The results of this first human gene therapy trial for RPE65 are incredibly encouraging, and are both safe and effective. Indeed, early results were so positive that all of the control subjects (people who did not receive the therapy during testing) opted to be treated following the study. This is good news for people living with inherited retinal diseases caused by mutations in the RPE65 gene.
Dr. Molday is now developing strategies to fix genes that are much larger than RPE65, including ABCA4, which is associated with Stargardt disease, and MYO7A, which is associated with Usher Syndrome. Along with an international team of researchers, Dr. Molday is designing new viral vectors that could be used to treat these diseases with gene therapy.
The team’s recent victory involved developing a successful strategy to express ABCA4 in photoreceptors. The approach combines two vectors, which together have the ability to express the gene and ultimately restore its function. Their exciting ‘proof-of-concept’ results, which show that their method can be used to express large genes inside photoreceptors, are game changing! They continue to work on optimizing this method in animal models, with a plan to move toward clinical trials.
Thanks to support from our donors, Dr. Molday and his team are expanding the range of retinal diseases that could be treated with gene therapies.