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Gene Therapy Could Cure Inherited Eye Disease In The Future

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Though a single treatment may not be enough, a study published on May 3rd in The New England Journal of Medicine suggests that gene therapy could improve eyesight for those born with a condition known as Leber congenital amaurosis (LCA) that causes sufferers to lose vision during childhood.

Scientists at the Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania treated patients with a single administration of the vector containing the gene RPE65. They found that improvement in the patients’ vision lasted between 5 and 6 years after treatment, peaked within 1 to 3 years, and then started diminishing.

The data published in the study was gathered from 3 of the 15 subjects who participated in the study. All 3 had similar results as researchers say “the treated retina showed improved visual sensitivity, which slowly increased in area and then contracted”.

The study also notes that “We observed a subsequent decline in the area of improved sensitivity in all patients; the decline in Patient 3 occurred earlier than in the other patients”. This could be valuable data since Patient 3 is also the one who showed improvement fastest –over the course of a year, compared with 1 to 3 years in Patient 2, and over three years for Patient 1.

Lead author Samuel G. Jacobson, M.D., Ph.D., professor of ophthalmology and director of the Center for Hereditary Retinal Degenerations and Retinal Function Department at Scheie Eye Institute, expressed his disappointment at the findings but also admitted it takes them a step closer to better cures:

“Gene therapy for LCA demonstrated we could improve vision in previously untreatable and incurable retinal conditions. Even though the current version of the therapy doesn’t appear to be the permanent treatment we were hoping for, the gain in knowledge about the time course of efficacy is an opportunity to improve the therapy so that the restored vision can be sustained for longer durations in patients”.

Jacobson and co-investigators Artur V. Cideciyan, PhD, research professor of ophthalmology at Penn and William W. Hauswirth, PhD, professor of ophthalmology at the University of Florida at Gainesville, started the study in 2007 and “within days of the [RPE65] injections, some patients reported increases in their ability to see dim lights they had never seen before. It was remarkable for us to get this feedback that things were indeed changing positively”.

They also noted that 4 of the 15 patients started relying on their fovea, a retinal area with high density of photoreceptors located near the gene therapy injection site for seeing letters. . The fovea is typically used for seeing fine details.

Dr. Cideciyan, the co-investigator who reported these findings, said that “For some patients, preferential use of the treated area for seeing letters came about spontaneously about a year after the gene therapy and remained functional for up to six years”.

Dr. Paul Sieving, director of the National Eye Institute, also acknowledges the importance of the study and that a gene therapy approach has a high change of improving vision in people with LCA once scientists gain a better understanding of it:

“As with any application of a novel therapy, it now needs to be fine-tuned. More research is needed to understand the underlying biology and how we can preserve or restore photoreceptors for a lifetime”.

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