Safety and efficacy of gene transfer for Leber's congenital amaurosis

N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27.

Abstract

Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blindness / congenital
  • Blindness / genetics
  • Blindness / pathology
  • Blindness / therapy*
  • Carrier Proteins / genetics*
  • DNA, Complementary
  • Dependovirus / genetics
  • Eye Proteins / genetics*
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Injections
  • Mutation
  • Promoter Regions, Genetic
  • Reflex, Pupillary
  • Retina / pathology
  • Retinal Degeneration / congenital
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy*
  • Visual Acuity
  • cis-trans-Isomerases

Substances

  • Carrier Proteins
  • DNA, Complementary
  • Eye Proteins
  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Associated data

  • ClinicalTrials.gov/NCT00516477