The National Eye Institute Launches Human Study for Retinoschisis Gene Therapy

March 03, 2015

The first-ever gene-therapy clinical trial for X-linked retinoschisis (XLRS), a vision-robbing retinal disease, was recently launched at the National Eye Institute (NEI), one of the federally funded National Institutes of Health.

XLRS is an inherited retinal condition that causes severe vision loss and blindness in males. As many as 140,000 people are affected worldwide. As an X-linked disease, it’s passed from mothers, who are unaffected carriers, to their sons. Each son has a 50 percent chance of inheriting XLRS. The condition is caused by mutations in the gene RS1 which lead to splitting of the layers of the retina.

“Our trial is Phase I/IIa, so the first question we’re addressing is safety,” says Paul Sieving, M.D., Ph.D., the trial’s lead investigator and director at the NEI. “After that step, we hope to learn whether the human biological response to the gene therapy follows the success we had in mice, and whether it can improve visual function.”  

Dr. Sieving previously published results for the XLRS mouse–model study in which the treatment closed cavities caused by the splitting of retinal layers. It also restored vision, even in adult animals.

The treatment involves replacement of defective copies of RS1 with those that are healthy. The therapeutic copies are inserted into a human-engineered virus, which penetrates the affected cells to deliver the genetic cargo. Known as an adeno-associated virus, or AAV, the delivery system is being used in other gene-therapy clinical trials, including those that have restored vision in people with Leber congenital amaurosis and choroideremia. Researchers believe a single dose of the treatment—which is injected into the vitreous, the gel-like substance in the middle of the eye— may work for several years, perhaps a lifetime.

“We are delighted by the launch of the NEI’s landmark study, which holds great promise for reversing blindness. It’s a major step forward for the greatly expanding field of retinal-disease therapies,” says Gordon Gund, chairman and co-founder at the Foundation Fighting Blindness. “The Foundation began funding Dr. Sieving more than 30 years ago, when he was an up-and-coming scientist investigating retinal conditions like retinoschisis. Thanks to his innovative work and perseverance, we’re now getting an emerging therapy for a challenging disease out to the people who need it.”

Dr. Sieving received a career development award from the Foundation in 1983, when he was a clinical fellow in genetic retinal degenerations under Eliot Berson, M.D., at Harvard Medical School’s Massachusetts Eye and Ear Infirmary. In 1985, he joined the Kellogg Eye Center at the University of Michigan. He was named director of the Foundation’s research center at Kellogg in 1989.

Applied Genetic Technologies Corporation (AGTC), a gene-therapy development company, is also planning a clinical trial for an XLRS gene therapy. The Foundation funded pre-clinical research at Oregon Health & Science University in support of AGTC’s clinical efforts for XLRS.

Details of the XLRS clinical trial at the NEI are listed on the NIH clinical trials website.