Retinitis Pigmentosa Cure Found Using Gene Therapy in Dogs
Retinitis pigmentosa, a blinding eye disease that is caused by the same genetic defect in both dogs and humans, was successfully corrected by a University of Pennsylvania research team that used gene therapy in afflicted dogs. The retinitis pigmentosa cure holds promise for eventual treatment in humans as well.
Dogs and humans have similar eye anatomy
Dogs are more than man’s best friend: the two species also share similar eye anatomy, physiology, characteristics of retinitis pigmentosa, and a positive response to the gene therapy used in this latest study.
Both humans and dogs can contract X-linked retinitis pigmentosa (XLRP), a disease that is caused by abnormalities in the RPGR gene. Approximately 100,000 people in the United States suffer with retinitis pigmentosa, a term that refers to a group of inherited eye diseases that cause degeneration of the retina.
What is retinitis pigmentosa?
Retinitis pigmentosa is mainly caused by defective genes that are inherited from one or both parents. Genetic mutations can be passed along to children through one of three different patterns: autosomal recessive, autosomal dominant, or X-linked. In families with X-linked retinitis pigmentosa, males develop the disease much more often and are more severely affected while females carry the trait and are less likely to experience vision loss.
In retinitis pigmentosa, the cells in the retina responsible for capturing images—called rods and cones called photoreceptor cells—die. This leads to a gradual decline in vision, and most people with retinitis pigmentosa are legally blind by age 40.
Gene therapy cured dogs with retinitis pigmentosa
In the new study, the researchers successfully treated dogs that had two different RPGR mutations, both of which impact photoreceptors in different ways. This form of blindness is rare in dogs, but it is common in people.
After a single subretinal injection of the therapeutic RPGR gene (a normal version of the gene found in humans) was given to affected dogs, the rods and cones repaired themselves and the photoreceptor connections to other retinal neurons also recovered.
The gene therapy treatment is complex and requires two critical factors: the right genetic tools and surgical skills to ensure the genes are delivered only to the diseased cells.
On the genetic front, the scientists had to choose a viral vector (a vehicle that delivers genetic material into a cell) that would target both cones and rods, but not other cells. They also needed to find a “promoter,” a piece of genetic code that would turn on the gene only when the virus entered the correct cell.
According to the study’s lead author, William Beltran, who is assistant professor of ophthalmology at Penn’s School of Veterinary Medicine, “Every single abnormal feature that defines the disease in the dogs was corrected following treatment.”
Beltran also noted in a release from the University of Pennsylvania that “not only can we prevent the disease onset but also restore the remaining photoreceptors cells to normal once the disease is ongoing.”
More positive news was reported by Gustavo Aguirre, senior author of the study and professor of medical genetics and ophthalmology at Penn Vet. He noted that their finding “not only provides hope for reversing XLRP but potentially for any form of photoreceptor degeneration.”