Using gene therapy, ophthalmology researchers from Penn's School of Veterinary Medicine have treated dogs with congenital achromatopsia, restoring their day vision in what appears to be a permanent cure for a form of blindness that also affects humans.
Achromatopsia is a rare, inherited form of total color blindness that affects the function of the cone photoreceptors in the retina. Cone function is essential for day and color vision, central visual acuity and therefore most daily visual activities.
The Penn treatment cured younger canines regardless of the mutation that caused their achromatopsia and was effective for at least the 33 months of the study. The successful therapy was documented through an imaging technique called electroretinography that showed the restoration of the cone function. The researchers also measured the dogs’ ability to negotiate a short obstacle course. A video shows dogs with this vision disorder successfully managing the obstacle course in the dark, but unable to get through it in light. After treatment, the dogs traverse the course in light with no problem.
The results represent the second successful cone-directed gene replacement therapy in achromatopsia animal models and the first outside of mouse models. The gene therapy, delivered directly to the retina, targets mutations of the CNGB3 gene, the most common cause of achromatopsia in humans. The results hold promise for future clinical trials of cone-directed gene therapy in achromatopsia and other cone-specific disorders.
"The successful restoration of visual function with virus-mediated gene replacement therapy has ushered in a new era of retinal therapeutics," said András M. Komáromy, assistant professor of ophthalmology at Penn Vet and lead author of the study.
Many vision-impairing disorders in humans result from genetic defects and to date mutations have been identified in approximately 150 genes out of approximately 200 mapped retinal disease loci. This wealth of genetic information has provided fundamental understanding of the multiple and specialized roles played by photoreceptors and the retinal pigment epithelium in vision, and how mutations in these genes result in disease. Together with the development of gene transfer technologies, it is now possible to realistically consider the use of gene therapy to treat these previously untreatable disorders.
Originally published on April 21, 2010.
Originally published on April 21, 2010