Gene augmentation trials using the Rpe65-deficient dog: Contributions towards development and refinement of human clinical trials

Abstract

Dogs with a spontaneous mutation in Rpe65 have been key in the testing of gene augmentation therapy using viral vectors to introduce a normal copy of the Rpe65 gene. These ground-breaking experiments have led to Phase I/II human clinical trials for treatment of Leber congenital amaurosis type II (LCAII). The Rpe65-deficient dog remains a useful model for studies to refine this treatment approach. A recent question it has been used to answer is whether or not immune response resulting from the gene augmentation treatment of one eye interferes with the success of the same treatment in the second eye. Fortunately, it was shown that treatment of the second eye had a similar success to that of the first eye, clearly demonstrating potential for gene augmentation therapy in the second eye of LCAII patients. © 2012 Springer Science+Business Media, LLC.