A novel form of gene therapy improved the vision of three patients with congenital blindness when treated in their second eye. The study, published in Science Translational Medicine, reported that the patients were able to see in dim light and two could navigate obstacles in low-light situations after receiving the same treatment in the other eye.

Scientists from the Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia (CHOP) led the study, which targeted Leber’s congenital amaurosis (LCA). The researchers injected patients with an adeno-associated viral vector that carried a normal version of the RPE65 gene, which is mutated in one form of LCA. Neither treatment triggered an immune reaction that cancelled the benefits of the inserted genes.

The researchers previously conducted a clinical trial of this gene therapy in 12 patients with LCA; four of them were children aged 11 and younger at the time of treatment. The researchers had treated only one eye—the one with worse vision. Six of the patients experienced improved vision enough to no longer be classified as legally blind.

“Patients have told us how their lives have changed since receiving gene therapy,” says study co-leader Jean Bennett, M.D., Ph.D., F.M. Kirby professor of ophthalmology at Penn. “They are able to walk around at night, go shopping for groceries and recognize people’s faces—all things they couldn’t do before. At the same time, we were able to objectively measure improvements in light sensitivity, side vision and other visual functions.”
Other objective results came from brain signals seen on neuroimaging. When a dimly-flickering checkerboard pattern flashed in front of a patient’s recently treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).

“This finding is telling us that the brain is responding to the eye’s sensitivity to dim light,” says Manzar Ashtari, Ph.D., a radiology researcher at CHOP and the study’s co-leader.

Bennett J, Ashtari M, Wellman J, et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012 Feb 8;4(120):120ra15.