Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years.

Objective: To determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene.

Design: Open-label, dose-escalation phase I study of 15 patients (range, 11-30 years of age) evaluated after subretinal injection of the rAAV2- RPE65 vector into the worse-functioning eye. Five cohorts represented 4 dose levels and 2 different injection strategies.

Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model.

Purpose: To investigate the human disease due to CRB1 mutations and compare results with the Crb1-mutant rd8 mouse.

Methods: Twenty-two patients with CRB1 mutations were studied. Function was assessed with perimetry and electroretinography (ERG) and retinal structure with optical coherence tomography (OCT).

Retinal disease in Rpe65-deficient mice: comparison to human leber congenital amaurosis due to RPE65 mutations.

Purpose: To quantify the retinal disease in Rpe65-deficient mice across a wide age span and compare the results to those in humans with Leber congenital amaurosis (LCA) caused by RPE65 mutations.

Methods: Full-field electroretinograms (ERGs) were recorded from wild-type (C57BL/6; Rpe65(+/+)) and Rpe65(-/-) mice at ages ranging from ∼1 month to 2 years. A physiologically based model of rod phototransduction activation was used to determine photoreceptor (P3) cell components of ERG photoresponses.