Research funded by the National Eye Institute has contributed to groundwork for moving gene therapy forward into clinical trials for people with blinding eye disorder, according to a news release. There is no cure for blinding eye disorder. However, gene therapy preserved vision in a study involving dogs with naturally occurring, late-stage retinitis pigmentosa, according to the release by the NEI, which is part of the National Institutes of Health.
Scientists from the University of Pennsylvania in Philadelphia and the University of Florida at Gainesville determined for the first time that gene therapy may be of potential benefit even after there has been significant loss of cells in the eye. Up to this point, animal studies had shown benefits from gene therapy only when it was used in the earliest stages of the disease. “The study shows that a corrective gene can stop the loss of photoreceptors in the retina, and provides good proof of concept for gene therapy at the intermediate stage of the disease, thus widening the therapeutic window,” Neeraj Agarwal, PhD, a program director at NEI, said in the release.
Retinitis pigmentosa is the most common inherited disease that causes degeneration of the retina, the light-sensitive tissue lining the back of the eye. Roughly 1 in 4,000 people are affected and about 10 to 20% have a particularly severe form called X-linked retinitis pigmentosa, which predominately affects males, causing night blindness by age 10 and progressive loss of the visual field by age 45.
To overcome the effects of mutations in the GTPase Regulator gene, which encodes a protein important for maintaining the health of photoreceptors. The researchers packaged healthy RPGR genes into an adeno-associated virus that is not known to cause any human diseases. The aim is for the virus to deliver the genes into retinal cells and for the genes to produce the RPGR protein.
The researchers then tested the gene therapy in a naturally occurring canine form of RPGR X-linked retinitis pigmentosa that appears among some mixed breeds. Dogs with early to late stages of the disease were treated with the therapy in one eye; the untreated eye was evaluated as the control. Their results are published in Proceedings of the National Academy of Sciences.
Serial imaging suggested that the therapy halted the thinning of the retinal layer where photoreceptors are located and that commonly degenerates from the disease, and suggested gene therapy halted disease-associated cell death for at least the length of the 2.5-year study.
Even in dogs with later-stage disease, gene therapy halted the loss of retinal thickness and preserved the structure of surviving photoreceptors. By contrast, untreated eyes continued to lose retinal thickness and photoreceptor function.
Before the therapy can be tested in people, additional research is needed to assess its safety and the risk for potential toxicity, said the study’s co-leaders, Gustavo Aguirre, VMD, PhD, and William Beltran, DVM, PhD, of the University of Pennsylvania. In the meantime, study collaborators, Artur Cideciyan, PhD, and Samuel Jacobson, MD, P.D., also at the University of Pennsylvania, are evaluating patients with RPGR mutations in preparation for a future clinical trial.
To comment, email [email protected]