Gene therapy rapidly improves night vision in adults with congenital blindness

New research from the Scheie Eye Institute shows success with a gene therapy that carries the DNA of the healthy version of the GUCY2D gene into the retina.

Adults with a genetic form of childhood-onset blindness experienced striking recoveries of night vision within days of receiving an experimental gene therapy, according to researchers at the Scheie Eye Institute in the Perelman School of Medicine.

Microscopic retinal images illustrating results from gene therapy on vision. — Upper left: Normal night vision depiction and a normal cross-sectional retinal image. Upper right: Reduced vision as a result of mutation in the GUCY2D gene. The near normal retinal image of the patient illustrates why gene therapy was originally recommended. Lower left: The gene therapy procedure shown as a subretinal injection. Lower right: Graph of night vision (rod visual function) improving dramatically over days following treatment (vertical axis is in log units). (Image: A. Sumaroka/University of Pennsylvania)

The patients had Leber congenital amaurosis (LCA), a congenital blindness caused by mutations in the gene GUCY2D. The researchers, whose findings are reported in the journal iScience, delivered AAV gene therapy, which carries the DNA of the healthy version of the gene, into the retina of one eye for each of the patients in accordance with the clinical trial protocol. Within days of being treated, each patient showed large increases, in the treated eye, of visual functions mediated by rod-type photoreceptor cells. Rod cells are extremely sensitive to light and account for most of the human capacity for low-light vision.

“These exciting results demonstrate that the basic molecular machinery of phototransduction remains largely intact in some cases of LCA, and thus can be amenable to gene therapy even after decades of blindness,” says study lead author Samuel G. Jacobson, a professor of ophthalmology at Penn.

LCA is one of the most common congenital blindness conditions, affecting roughly one in 40,000 newborns. The degree of vision loss can vary from one LCA patient to another but all such patients have severe visual disability from the earliest months of life.

To the researchers, the results confirm that GUCY2D gene therapy to restores rod-based photoreceptor functions—and suggest that GUCY2D–LCA patients with more severe rod-based dysfunction are likely to benefit most dramatically from the therapy. The practical message is that there should be an emphasis on rod vision measurements at screening of LCA candidates and in monitoring them throughout a treatment trial.

The findings also underscore the fact that in some patients with severe congenital vision loss, the retinal cell networks that mediate vision remain largely alive and intact, and need only the resupply of a missing protein to start working again, more or less immediately.

This story is by Julie Wood. Read more at Penn Medicine News.