A successful gene therapy treatment which stops late-stage retinitis pigmentosa (RP) in dogs could lead to trials in humans with the condition, according to new research from US scientists.
The findings come from a team of researchers from the University of Pennsylvania, who studied canine X-linked RP, which has a similar disease course to the human form of the condition. The disease starts early in life and leads to the progressive loss of vision due to a loss of photoreceptors.
X-linked RP (XLRP) is a recessive condition, typically caused by a faulty copy of the RPGR gene which is located on the X-chromosome. It particularly affects males, who lack a second X-chromosome, and so lack a second copy of the gene which could mask the effects of the faulty copy.
In previous trials in 2012, researchers used a virus to deliver functional copies of the gene to photoreceptors in dogs, as a preventative treatment for the disease. The trials proved successful in early stage disease.
“Now we've gone further, showing that the treatment is long-lasting and effective even when started at mid- and late-stage disease,” said Dr William A. Beltran, associate professor of ophthalmology at the university and co-lead author of the study.
In the recent trials, the group treated animals at later stages of disease, where as much as 40–60% of the photoreceptors had already been lost.
They found that the gene therapy stopped photoreceptors in the treated area from dying and prevented vision loss in the animals for more than two years. Dogs performed better on vision-based assessments and the treatment was even found to reverse some of the abnormal changes to photoreceptors caused by the condition, improving the structure of the retinal cells.
Dr Beltran added: “What the dog studies show, especially those that are treated at a later stage, is that you can treat a relatively small region – 20% or less of the retinal surface, where you already had 50% of photoreceptor cells that died before treatment – and still see not only an electrophysiological improvement and rescue but an actual rescue of visual behaviour.”
The researchers are reported to be reviewing patients to find suitable injection sites in the retina and to determine which patient types could potentially be recruited for a clinical trial.
Professor William W. Hauswirth, a researcher at the University of Florida and one of the study’s authors, said: “Based on my experience developing gene therapies in animal models for many other inherited retinal diseases, I believe this report describes perhaps the strongest case yet for eventual successful therapy in humans for XLRP.”
The findings are published in Proceedings of the National Academy of Sciences.
Image credit: Flickr/Christine and David Schmitt