Gene therapy to treat retinal degenerations is alive and well. Dozens of centers around the world are studying subretinal and intravitreal gene delivery, and more than 1,000 patients are enrolled in trials.
When considering accomplishments recorded in the arena of gene therapy, the “firsts” are impressive.
Voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics) was the first gene therapy to receive FDA approval and EU approval to treat an inherited disease—Leber’s congenital amaurosis (LCA), an autosomal recessive blindness—in the United States and Europe.
The clinical trial of voretigene neparvovec-rzyl was the first to enroll pediatric subjects with a non-lethal disease.
The drug, according to Jean Bennett, MD, PhD, was the first to develop a path for the development of genetic treatments for blindness and provided motivation for ophthalmologists and insurers to carry out genetic testing.
Dr. Bennett is director of the Center for Advanced Retinal and Ocular Therapeutics, professor of ophthalmology and professor of Cell and Development Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Over the previous three decades, seeval vehicles to deliver gene therapy have been tested; the one that stood out in many studies was the adeno-associated virus (AAV), a single-strand virus that is not disease-causing in animals or humans and can infect post-mitotic neurons and dividing cells, Dr. Bennett said.
When injected by subretinal injection, the AAV vector delivers the promoter and the gene under study, and this blueprint ultimately makes its way to the nucleus as a stable episome.
“There has been huge progress over the years,” she said. “There are now 271 genes identified that, upon mutation, cause retinal degeneration.”
RPE65 was identified as being mutated in 2007 in humans with early-onset retinal degeneration. Many spontaneously mutant and genetically engineered animal models are also under study.