Gene therapy halts sight loss in dogs with late-stage retinitis pigmentosa

Results from a new study show that vision can be preserved even at a late stage in a severe inherited eye disorder. The proof-of-concept findings move gene therapy for X-linked retinitis pigmentosa a step closer to human clinical trials.

Retinitis pigmentosa is the most common group of inherited conditions to affect the light-sensitive layer of tissue at the back of the eye (the retina). X-linked retinitis pigmentosa is a particularly severe type. It’s caused by faults in certain genes on the X chromosome (one of the two sex chromosomes) which means it usually affects men. Sight loss begins in childhood with legal blindness by the age of 45.

In the current study, researchers from the USA engineered a harmless virus to carry a healthy copy of a gene called RPGR. About 7 in 10 people with X-linked retinitis pigmentosa have faults in this gene.

Dogs with a naturally-occurring version of the condition were treated with the gene replacement therapy in one eye only. The other eye served as a control.

Useful vision

Images and recordings of electrical activity from the retina showed that the light-detector cells (photoreceptors) kept a better structure and continued to work, compared to the untreated eye. This was true in dogs with both early- and late-stage disease. The dogs were also better at finding their way through a maze and obstacle course when using the treated eye. This shows that the treatment gave them useful vision.

“There is still a way to go in terms of testing safety and effectiveness before this treatment can be taken to human clinical trials,” said Dr Dolores M Conroy Director of Research at Fight for Sight. “But it’s very interesting to see the therapeutic window for this gene therapy extended to animals in the later stages of disease, after significant photoreceptor loss, as we’ve previously only seen benefits from treatment in the earliest stages.”

Fight for Sight research

The results are published in the journal PNAS. One of the study authors has been collaborating with Fight for Sight-funded PhD student Xun Zhang who is in Dr Xinhua Shu’s lab at Glasgow Caledonian University. The team is working on making the RPGR gene therapy technique even better and will first test it in mice. Results from the project are due early in 2017.