XLRP Gene Therapy Rescues Vision in Late-Stage Disease

October 20, 2015

Foundation-funded researchers from the University of Pennsylvania have found that an emerging gene therapy for X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene RPGR preserves vision in canines with late-stage disease. The research, reported in the Proceedings of the National Academy of Sciences, provides hope that the treatment might not only benefit people with early and intermediate stages of the disease, but those with more advanced vision loss as well.

The biotech company Applied Genetic Technologies Corporation (AGTC) is working toward a clinical trial of an XLRP (RPGR) gene therapy. The University of Pennsylvania research team, led by William Beltran, V.M.D., Ph.D., Gus Aguirre, V.M.D., Ph.D., and Artur Cideciyan, Ph.D., is providing proof of concept for the treatment.

“This is an important finding, because it suggests there may be a larger window of opportunity to save vision in humans with this devastating retinal condition for which there are no treatments,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness.

In 2012, the University of Pennsylvania investigators showed that the emerging treatment worked at an early stage of disease, when retinal degeneration begins. Vision was rescued for more than six months in that study, and now the current study extends it to more than three years.

In their newly published study for late-stage disease, the treatment rescued vision for more than two years. The therapy was administered when the canines had lost 40 to 60 percent of their photoreceptors.

“XLRP caused by RPGR mutations leads to a similar, fast rate of retinal degeneration and vision loss in dogs and humans,” says Dr. Beltran. “Encouraging results from our canine study suggest that the gene therapy has the potential to save remaining vision in humans even when intervening at later stages of the disease."

The researchers will continue to monitor some of the dogs, but based on their analysis of the treated retinas thus far, they believe the disease process has been halted.

“The ability of the gene therapy to prevent photoreceptor loss at early, intermediate and late stages of the disease in the dog model of X-linked retinitis pigmentosa is tremendously exciting news”, says Jeffrey D. Chulay, M.D., chief medical officer at AGTC. “This study is an important step toward the goal of developing treatments for patients with XLRP.” 

The candidate gene therapy uses a human-engineered adeno-associated virus, or AAV, to deliver healthy copies of the RPGR gene to rods and cones, the cells that make vision possible. Researchers believe a single treatment, contained in a tiny drop of liquid injected underneath the retina, will last years. William Hauswirth, Ph.D., of the University of Florida developed the AAV, which is similar to the one used in gene-therapy clinical trials for Leber congenital amaurosis.

Other members of the XLRP gene therapy team include Samuel Jacobson, M.D., Ph.D., at the University of Pennsylvania, and Al Lewin, Ph.D., at the University of Florida.

AGTC has not begun recruiting for its planned XLRP gene therapy clinical trial. Individuals and families with retinal diseases who want to be notified about upcoming clinical trials for which they may qualify can register at My Retina Tracker, the Foundation’s free and secure patient registry.