National Eye Institute Science Advance

Clinical Trial of Gene Transfer Therapy for Congenital Eye Disease Finds Lasting Visual Improvement

Background:
In 2007, the National Eye Institute launched a phase I clinical trial to assess the safety of gene transfer in humans with a form of Leber congenital amaurosis (LCA). This is the first clinical trial to assess gene therapy in humans with eye disease. People with LCA are born with severe visual impairment or lose their vision in early childhood. The form of LCA being evaluated in this study results from mutations in the RPE65 gene which plays a critical role in the visual cycle, the set of biochemical reactions that convert light into an electrical signal to initiate vision. Mutations in the RPE65 gene disrupt the visual cycle resulting in LCA. Fortunately, the structure of the retina remains relatively intact into early adulthood, providing an opportunity to intervene therapeutically.

In 2009, investigators published one year follow-up results of the three patients who received this investigational therapy. The patients, ranging in ages from 22-25 years, remained healthy and experienced no adverse events. Statistically significant increases in light sensitivity were found in the first three months of the trial in all patients and remained unchanged at one year. Rigorous clinical examinations corroborated that the visual improvements were found in the treated area of the retina, lending further objective evidence of the treatment's efficacy. These data also correlate with subjective reports by patients of improved vision. This landmark clinical trial will next evaluate gene transfer in younger patients with less severe disease, which may prove more efficacious.

Public Impact Statement/Significance:
Gene transfer is particularly well-suited to the treatment of retinal degenerative diseases. Nearly 200 single gene defects have been implicated in these diseases. This clinical trial is an important step in treating LCA and in establishing proof-of-concept for gene transfer as a viable therapy for an entire family of eye diseases. This trial, and similar studies by two other independent groups, was enabled by more than 15 years of NEI support of basic research and preclinical studies of RPE65 and gene transfer for treating blinding diseases.

Grant Support:
U10EY017280-01 Clinical Trials of Gene Therapy for Leber Congenital Amaurosis.

Publication Citation

• Cideciyan, A.V., et al. Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther. 2009 Sep; 20(9):999-1004. PubMed
• Cideciyan, A.V., et al. Vision 1 year after gene therapy for Leber's congenital amaurosis. N Engl J Med. 2009 Aug 13; 361(7):725-7. PubMed

Learn more about gene therapy for LCA.

Last Reviewed: January 2010