An inherited eye disease called retinitis pigmentosa (RP) impacts roughly one of every 3,500 Americans; it disrupts the cells in the retina, which is a vital, light-sensitive lining in the eye. Peripheral and nighttime vision suffers when it begins to break down. Researchers at University of Florida Health and Penn Medicine have now developed a way to treat this devastating disorder with gene therapy. Reporting in the Proceedings of the National Academy of Sciences, the team successfully improved eyesight in animals that were afflicted with RP.
"We've known for decades that this specific molecule causes a specific form of retinitis pigmentosa, but developing a treatment has not been straightforward," explained co-lead author Dr. Artur V. Cideciyan, research professor of ophthalmology at Penn Medicine. "Now, with these elegant results based on years of study in dogs, we can start working toward treating these mutations and prevent deterioration of photoreceptor cells in humans."
In this work, a tool called an adeno-associated virus, or AAV, was used to deliver the gene therapy, which in this case replaces a mutant copy of the rhodopsin gene with a normal copy, thereby saving photoreceptor cells (as explained in the video). The virus has been demonstrated as safe in a rodent model and in humans in previous studies.
"We were able to save cone vision in the dogs," said Dr. Alfred Lewin, a professor in the UF College of Medicine's department of molecular genetics and microbiology and a member of the UF Genetics Institute. "If we can do that in people, it will save the central vision that allows them to recognize faces, read and watch television."
After UF Health scientists created the therapeutic, scientists at Penn treated ten beagles with RP. After nine weeks, mutant gene levels had been significantly reduced in areas of the eye that had been treated. After eight months, other photoreceptor cells - rods - in the retina were also protected.
"It's a one treatment fits all," noted co-lead author William A. Beltran, a professor of ophthalmology at Penn's School of Veterinary Medicine. "The treatment targets a region of the rhodopsin gene that is homologous in humans and dogs and is separate from where the mutations are located. That gives us great hope about making this a translational treatment."
Lewis is hopeful that this technology can be extrapolated to treat other genetic mutations that cause blindness, and maybe even single gene mutations that impact other organs like the kidney and liver.
For now, this work will continue so that the exact dosage can be refined.