Gene therapy trial sees massive improvement in vision

The vision of people with a rare inherited condition that causes them to lose much of their sight early in childhood was 100 times better after they received gene therapy to address the genetic mutation causing it. Some patients even experienced a 10,000-fold improvement in their vision after receiving the highest dose of the therapy, according to researchers from the Perelman School of Medicine who co-led the clinical trial published in The Lancet.

"That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment," says the study's lead author, Artur Cideciyan, a research professor of ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. "One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire."

A total of 15 people participated in the Phase 1/2 trial, including three pediatric patients. Each patient had Leber congenital amaurosisas the result of mutations in the GUCY2D gene, which is essential to producing proteins critical for vision. This specific condition, which affects less than 100,000 people worldwide and is abbreviated as LCA1, causes a significant amount of vision loss as early as infancy.

Improvements were noticed quickly, often within the first month, after the therapy was applied and lasted for at least 12 months. Observations of participating patients are also ongoing. Three of six high-dosage patients who were tested to navigate a mobility course in varying levels of light achieved the maximum-possible score. Other tests used eye charts or measured the dimmest flashes of light patients perceived in a dark environment.

Of the nine patients who received the maximum dosage, two had the 10,000-fold improvement in vision.

"Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients' photoreceptors would be to treatment after decades of blindness," says Cideciyan. "It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious."

Read more at Penn Medicine News.