Mutations in RPE65 and LRAT cause both RP and LCA in humans where two key enzymes of the visual cycle, retinoid isomerase (RPE65) and lecithin:retinol acyltransferase (LRAT), are missing which cause severe impairment in rod photoreceptor function. These patients suffer from severe vision loss or eventual total blindness.
Currently, the only approved treatment for patients with RPE65 mutations is LUXTURNA® (voretigene neparvovec-rzyl) in the United States and the European Union. There are no approved treatments for LRAT mutations. LUXTURNA® is a gene therapy administered through subretinal injection into the diseased eye. Besides the high cost and the need to perform surgery and inject each eye separately, only about 15-25% of the injected retina is treated which leads to limited vision recovery. Long-term safety follow-up studies have reported adverse reactions including dyschromatopsia, glare, and probable surgery-related macular scar and thinning.1 Therefore, an unmet needs exist for non-surgical, bilateral treatment of retinal dystrophies secondary to RPE65/LRAT mutations at improved cost.