Researchers Identify Regions in the Retina to Target Therapies for Certain RP Patients
University of Pennsylvania investigators studied retinas of patients and canines with retinitis pigmentosa caused by mild mutations in RHO
When evaluating an emerging retinal gene therapy in a clinical trial, researchers need to administer it in a region where it will have a relatively quick and measurable effect on the patient’s vision. Because of the limited duration of clinical trials to minimize their cost, investigators usually need to know in a year or two if a therapy is saving or restoring vision.
Led by Artur Cideciyan, PhD, a Foundation-funded research team at the University of Pennsylvania recently published a study in the journal Nature Scientific Reports that may greatly inform where a future gene therapy may be administered for people with retinitis pigmentosa (RP) caused by mild mutations in the gene RHO. They identified a retinal transition zone (TZ) — a region where surviving rod photoreceptors have reduced function — in people and canines with mild RHO mutations. They believe that targeting rods in the TZ with gene therapy will have a relatively quick and measurable impact on a patient’s vision.
Rods are the photoreceptors that provide peripheral vision and vision in dark settings. In most people with RP, rods are affected first. Loss of cones — the photoreceptors that provide the ability to read, recognize faces, and see in lighted settings — usually occurs later in the disease. Researchers believe that saving rods can help preserve cones.
“The University of Pennsylvania team conducted a very meticulous study, which followed the progression of disease for more than for 20 years in some patients. A key finding was that while progression may be slow in general for those with mild RHO mutations, there may be areas of the retina where disease is more rapid. The understanding of the structural changes caused by retinal degenerations are critical for clinical trial design and future treatment administration,” says Brian Mansfield, PhD, executive vice president for research and interim chief scientific officer at the Foundation Fighting Blindness. “Researchers can develop a very powerful therapy, but if they don’t know where to deliver it in the retina, the therapy will never make it through the human study.”
Iveric bio, a retinal disease biotech, is developing a gene therapy for people with RP caused by RHO mutations.
ProQR, a developer of RNA therapies, has a Phase 1/2 clinical trial underway of an RNA therapy for people with RP caused by the P23H mutation in RHO.
The University of Pennsylvania research team for the RHO study also included: William Beltran, VMD, PhD, Gustavo Aguirre, VMD, PhD, Sam Jacobson, MD, PhD, Alexander Sumaroka, PhD, Jason Charng, PhD, Malgorzata Swider, PhD, Alejandro J. Roman, MS, Vivian Wu, MS, and Brianna Lisi, BS