Leber Congenital Amaurosis (LCA) and Retinitis pigmentosa (RP) Caused by RPE65/LRAT Mutations

Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration and Leber congenital amaurosis (LCA) is a severe inherited form of retinal degeneration.


RP and LCA each have a prevalence of approximately 1 in 3,000-4,000 and 1 in 33,000 live births worldwide, respectively. About 5% of RP patients and 10% of LCA patients have mutations in the LRAT or RPE65 genes.

Tunnel Vision

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.


  1. “Study investigates safety, efficacy of LUXTURNA in real-world clinical practice,” Ocular Surgery News, September 23, 2021. https://www.healio.com/news/ophthalmology/20210923/study-investigates-safety-efficacy-of-luxturna-in-realworld-clinical-practice.
Fundoscopic image of a normal retina
Retina fundoscopic image of a patient with RPE65 mutation