Nearly two decades ago, a gene therapy restored vision to Lancelot, a Briard dog who was born with a blinding disease. This ushered in a period of hope and progress for the field of gene therapy aimed at curing blindness, which culminated in the 2017 approval of a gene therapy that improved vision in people with Leber congenital amaurosis (LCA), a rare, inherited form of blindness closely related to the condition seen in Lancelot. It represents the first FDA-approved gene therapy for an inherited genetic disease.
The gene therapy, which provides a functional copy of the RPE65 gene, has improved vision in patients, allowing them to experience the world in a way they never would have otherwise. But questions remain about how long-lasting these improvements will be and whether progressive degeneration of vision cells have been halted with the therapy.
In a new paper in the journal Molecular Therapy, researchers from the University of Pennsylvania turned back to canines to learn more about the factors that determine the outcome of gene therapy; this time, they treated dogs at more advanced stages of the disease, timepoints at which human patients are more likely to be treated. They discovered that dogs that were provided the therapy when more than 63% of their photoreceptor cells were still present but nonfunctional had great success. The effect of the treatment seemed lifelong, and there was an arresting of the progressive degeneration. But for those dogs that had lost more than half of their photoreceptor cells before receiving the treatment, the disease seemed to continue to progress, despite a short-term restoration of sight.
“Earlier work by our group and others had suggested that if you treated the disease at a time when the retina was degenerating, that degeneration continued, in people and in dogs,” says Gustavo D. Aguirre of Penn’s School of Veterinary Medicine. “This was in spite of short-term gains in vision. We wanted to follow up to get details about the extent of retinal degeneration that would still be compatible with a lasting effect.”
Fortunately, the lab had access to data that would help answer that question.