Scientists from Michigan State University and three collaborating universities around the globe were awarded an $8.2 million grant from the National Institutes of Health (NIH), which will allow them to expand on promising gene therapy for progressive retinal atrophy (PRA) in dogs. This solution then may be translated into a therapy for retinitis pigmentosa (RP) in humans.

PRA is an inherited condition that causes blindness in dogs, and results from mutations in the same genes that cause RP, an important hereditary cause of blindness in humans. The collaborative team has developed an effective therapy for PRA in dogs due to a mutation in the gene called cyclic nucleotide-gated channel b 1 (CNGB1). Humans have RP due to mutations in the same gene; this grant aims to further refine the therapy so it can be used in a clinical trial in RP patients.

“We’ve already published that the disease in dogs looks very much like the disease in humans and progresses in a very similar fashion, and we were able to perform gene therapy that, following an injection into the eye, effectively restored vision to the dogs with mutations in CNGB1,” says Dr. Simon Petersen-Jones, lead principle investigator and Myers-Dunlap Endowed Chair in Canine Health for the Department of Small Animal Clinical Sciences at the Michigan State University College of Veterinary Medicine. “This award will allow us to build on our primary gene therapy studies in preparation for an eventual clinical trial in human patients, which will follow the completion of the grant.”

For the grant, which will last for five years, scientists will:

• Optimize the viral vector for safe and effective delivery
• Perform the regulatory steps needed for approval by the US Food and Drug Administration of the viral vector as an investigational new drug
• Enroll human patients with RP due to CNGB1 mutations and use state-of-the-art techniques to study the progression of the changes in their eyes to identify biomarkers that can then be used to assess the effectiveness of treatment during a future clinical trial
• Finalize the product to meet good manufacturing practices and standards for a clinical trial

For this research, Petersen-Jones, DVet Med, PhD, DECVO, worked with Bill Hauswirth, PhD, Maida and Morris Rybaczki Eminent Scholar Chair in Ophthalmic Sciences at the University of Florida, who specializes in gene therapy; Stylianos Michalakis, PhD, head of the Retinal Gene Therapy Group at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University Munich, Germany, who is an expert regarding the protein that is defective in the canine patients, and has performed successful gene therapy in a murine model; and Stephan Tsang, MD, PhD, retina specialist at Columbia University in the City of New York at the CUMC/Edward S. Harkness Eye Institute with expertise in a range of inherited retinal diseases in humans, and will coordinate the detailed study of the progression of the condition in human patients. The team also has several additional collaborators in both the US and Europe.

“We have assembled an outstanding international team of top scientists and clinicians who will be able to collaborate to achieve our goal of developing an effective treatment for retinitis pigmentosa due to mutations in CNGB1. The therapy works extremely well in dogs, and we hope that this work will lead to the treatment being just as effective in human patients,” says Petersen-Jones.

For more information regarding PRA, visit the Petersen-Jones Laboratory webpage.