Gene Therapy for Vision

Luxturna and the gene therapy frontier

Overview

Gene therapy for vision aims to treat inherited eye diseases by delivering functional genes or editing faulty ones in retinal cells. The eye is well suited to this approach because it is small and accessible, is partly shielded from the immune system, and allows treatment effects to be measured directly, with the untreated eye often serving as a comparison. The landmark therapy is voretigene neparvovec, marketed as Luxturna, approved in the United States in 2017 for retinal dystrophy caused by mutations in both copies of the RPE65 gene, a cause of Leber congenital amaurosis and some forms of retinitis pigmentosa. It uses an adeno associated virus vector, delivered by subretinal injection during vitrectomy surgery, to restore a protein needed for the visual cycle, improving light sensitivity and navigation in dim light. Other inherited conditions investigated in clinical trials include choroideremia, X linked retinitis pigmentosa, X linked retinoschisis, achromatopsia, and Leber hereditary optic neuropathy, with mixed results. CRISPR based gene editing has also been tested in people with CEP290 related Leber congenital amaurosis, and optogenetic approaches seek to make surviving retinal cells sensitive to light regardless of the underlying gene defect.