First Patient Treated in XLRP Gene Therapy Clinical Trial

A 29-year-old British man is the first person to be treated in a gene therapy clinical trial for X-linked retinitis pigmentosa (XLRP). Robert MacLaren, MD, the lead investigator for the trial taking place at the Oxford Eye Hospital in the United Kingdom, says the patient is doing well and has gone home. The trial is being run by Nightstar, a biopharmaceutical company in the U.K. developing therapies for inherited retinal diseases. As many as 24 patients will be enrolled in the 12-month trial.

XLRP is a leading cause of inherited, progressive vision loss. The condition usually affects males, but is also diagnosed occasionally in females. Mutations in the gene RPGR cause about 70 percent of XLRP cases. RPGR mutations affect about 15,000 people in the United States and tens of thousands more around the world. The Nightstar gene therapy involves injection of healthy copies of RPGR underneath the retina. The RPGR copies are contained in a human-engineered virus — known as an adeno-associated virus or AAV — which is designed to readily penetrate retinal cells to deliver the therapeutic genetic cargo. While the current clinical trial is focused on evaluating safety, researchers hope that a single injection of the XLRP gene therapy will slow or halt vision loss for several years. Dr. MacLaren says the treatment was challenging to develop, because even the therapeutic copies of RPGR are prone to mutations. “The natural RPGR gene sequence is very difficult to read and reproduce,” he says. “But the new DNA sequence we are using has proven to be very stable in our laboratory studies. Dr. Dominik Fischer and other members of my team in Oxford spent many years working out how to develop a safe and effective gene therapy by manipulating the DNA sequence, but without changing the protein.” “We are delighted to see a gene therapy for XLRP move into a human trial. This is great news for many of our constituents,” says Stephen Rose, PhD, chief research officer, Foundation Fighting Blindness. “While most forms of RP lead to significant vision loss, XLRP tends to be on the severe end of the RP spectrum. We desperately need treatments to halt this challenging disease and look forward to learning more about this therapy’s potential as the trial progresses,” Rose says. Nightstar is also running a gene therapy clinical trial for choroideremia, an inherited retinal disease that causes severe vision loss in males. The company reported that the choroideremia gene therapy has provided vision improvements, sustained for 3.5 years, in five of the first six patients treated. Dr. MacLaren is also the lead investigator in that study.