Researchers Find Potential New Gene Therapy for Blinding Disease

Scientists funded by the National Eye Institute report a novel gene therapy that halts vision loss in a canine model of a blinding condition called autosomal dominant retinitis pigmentosa (adRP). The strategy could one day be used to slow or prevent vision loss in people with the disease.

“We’ve developed and shown proof-of-concept for a gene therapy for one of the most common forms of retinitis pigmentosa,” said Dr. William Beltran of the University of Pennsylvania School of Veterinary Medicine, a lead author of the study, which appeared online Aug. 20 in the Proceedings of the National Academy of Sciences.

Retinitis pigmentosa refers to a group of rare genetic disorders that damage light-sensing cells in the retina known as photoreceptors. Rod photoreceptor cells enable vision in low light and require a protein called rhodopsin for their light-sensing ability. People with adRP caused by mutations in the rhodopsin gene usually have one good copy of the gene and a second, mutated copy that codes for an abnormal rhodopsin protein. The abnormal rhodopsin is often toxic, slowly killing the rod cells. As the photoreceptors die, vision deteriorates over years or decades. Scientists have identified more than 150 rhodopsin mutations that cause adRP, challenging efforts to develop effective therapies.

The research team generated a gene therapy construct that knocks down the rod cells’ ability to produce rhodopsin using a technology known as shRNA (short-hairpin RNA) interference.

Gene therapy introduces genetic material, like shRNA, into cells to compensate for abnormal genes or to make a beneficial protein. Often adapted from viruses, vectors are engineered to effectively deliver this genetic material into cells without causing disease.

“The beauty of this novel gene therapy product is in its elegant vector design. I hope it works as well in humans, too,” said Dr. Neeraj Agarwal, translational research program director at NEI.