|
 Members of a University of Pennsylvania research team have shown that they can prevent, or even reverse, a blinding retinal disease, Xlinked Retinitis Pigmentosa, or XLRP, in dogs. The disease in humans and dogs is caused by defects in the RPGR gene and results in early, severe and progressive vision loss. It is one of the most common inherited forms of retinal degeneration in man. "Every single abnormal feature that defines the disease in the dogs was corrected following treatment," said lead author William Beltran, assistant professor of ophthalmology at Penn’s School of Veterinary Medicine. "We were thrilled," said senior author Gustavo Aguirre, professor of medical genetics and ophthalmology at Penn Vet. "The treated cells were completely normal, and this effect resulted from introducing the normal version of the human gene into the diseased photoreceptor cells."
The similarities between humans and dogs, in terms of both eye anatomy, physiology, disease characteristics and positive response to this gene therapy, raise hope for a clear path to human therapies. Beltran and Aguirre collaborated with Artur Cideciyan and Samuel Jacobson at the Scheie Eye Institute, part of the University of Pennsylvania’s Perelman School of Medicine. This achievement results from more than 10 years of close collaboration between the scientists at Penn’s veterinary and medical Schools and the University of Florida. In addition to others at Penn Vet, Scheie and Florida, researchers at the universities of Michigan and Massachusetts and the National Eye Institute at the National Institutes of Health contributed to the research.
The study will be published in the journal Proceedings of the National Academy of Sciences.
The gene therapy approach used takes advantage of a viral vector - a genetically modified virus that doesn’t cause disease and is unable to divide to deliver the therapeutic RPGR gene specifically to diseased rods and cones. In the absence of treatment, these cells malfunction and progressively die. The research team has previously successfully applied a similar approach to two other heritable vision disorders that occur in both humans and dogs: Leber congenital amaurosis and achromatopsia. The present study was more challenging, as it was necessary to target both main classes of photoreceptor cells.
While the exact disease mechanism of the RPGR form of XLRP is still unknown, the researchers were able to successfully treat dogs with two different RPGR mutations. The mutations disrupt photoreceptors in different ways, but both ultimately cause them to become useless for vision. While this form of blindness is rare in dogs, it is common in humans. Patients with XLRP usually begin to lose night vision as children and become almost totally blind by middle age. This is the first proof that this condition is treatable in an animal model; a single subretinal injection administered to the diseased dogs led to functional and structural recovery. The dogs’ recovery was assessed using a variety of methods that are used clinically in patients, such as electroretinography and optical coherence tomography. The researchers feel the results are promising and relevant for translation to the clinic.
|
