The two-year results of the Phase I/II, multi-center HORIZON clinical trial of the new subretinal gene therapy drug AGTC-501 for X-linked retinitis pigmentosa were recently published in the American Journal of Ophthalmology. Texas Retina’s Rajiv Anand, MD, serves as an investigator for this ongoing, five-year study evaluating the drug’s safety and efficacy, along with David Birch, PhD, Scientific Director at the Retina Foundation of the Southwest (Retina Foundation) in Dallas, and leaders at three other centers in the United States.
Understanding X-linked Retinitis Pigmentosa
The most common inherited retinal disorder, retinitis pigmentosa changes how the retina responds to light, making it hard to see. It causes some photoreceptor cells to gradually fade and die, losing the ability to transmit visual messages to the brain. This degeneration can lead to night blindness, visual field loss and eventually, blindness.
X-linked retinitis pigmentosa primarily affects men because of its X-linked inheritance pattern and often results from a mutation in the RPGR ORF15 gene.
“It accounts for approximately 15% of retinitis pigmentosa cases and is usually associated with an earlier onset and more severe disease, including legal blindness by around age 45,” shares Dr. Anand. “There is currently no effective treatment.”
About the HORIZON Study
With the open-label, multicenter, dose-escalation HORIZON study, a recombinant adeno-associated viral (rAAV2tYF) vector is used to deliver AGTC-501, a functioning gene copy of the full-length RPGR protein, directly to the photoreceptor cells via subretinal injection.
“Most of the Phase II patients underwent surgery at Texas Retina and were followed jointly at Texas Retina and the Retina Foundation,” explains Dr. Anand. “The surgery involves injection of the modified replacement gene solution in a carefully controlled bubble under the macula during surgery.”
The patients in the study were treated in one eye, and the other non-treated eye served as the control since the disease is bilateral. In the eyes that received the gene treatment under the central retina (macula), the vision and retina function improved over the two-year follow-up while the control eye continued to deteriorate.
“This is the first time that the gene therapy has stopped the vision loss and actually shown improvement in this progressively blinding disease,” says Dr. Anand.
The same treatment trial has been expanded. Texas Retina and the Retina Foundation are now conducting the DAWN and VISTA clinical trials with Dr. Anand and Dr. Birch serving as investigators.
Click here to access the full journal article or here to learn about all the clinical trials currently available at Texas Retina.
About Dr. Anand
Dr. Anand sub-specializes in medical retina, vitreoretinal surgery and ocular oncology, and has served Texas Retina for more than 30 years. He cares for patients in the Dallas Main, Dallas North, Denton and Plano offices. You can learn more about him here.