Effect of gene therapy on visual function in Leber's congenital amaurosis

N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27.


Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].).

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • 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
  • Retina / pathology
  • Retina / physiopathology
  • Retinal Degeneration / congenital
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy*
  • Visual Acuity
  • cis-trans-Isomerases


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

Associated data

  • ClinicalTrials.gov/NCT00643747