Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

TLDR

Early‑onset, severe retinal dystrophy caused by RPE65 mutations leads to poor vision at birth and complete vision loss in early adulthood. The study delivered subretinal injections of recombinant AAV2/2 carrying RPE65 cDNA driven by a human RPE65 promoter to three young adults. The therapy was well tolerated with no serious adverse events, did not change visual acuity, peripheral fields, or ERG in all patients, but one patient showed marked improvement in microperimetry, dark‑adapted perimetry, and subjective visual mobility, supporting further trials. ClinicalTrials.gov identifier NCT00643747.

Abstract

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]... ).