Cone-Rod Dystrophy Gene Therapy Rescues Vision in Canines

October 10, 2013

A French research team led by Fabienne Rolling, Ph.D., of INSERM, has used gene therapy to restore vision in a canine model of cone-rod dystrophy caused by mutations in the gene RPGRIP1. Reported in the journal Molecular Therapy, the advancement marks the first time RPGRIP1 gene therapy has been used successfully in a large-animal model of cone-rod dystrophy. Demonstration of safety and efficacy in a large animal is an important step in moving the therapy into human studies. Dr. Rolling says that her team is now adapting the RPGRIP1 for evaluation in humans.

In humans and the canine model, cone-rod dystrophy affects cones first, leading to loss of visual acuity and color vision in childhood. Loss of peripheral and night vision follow as the disease progresses and affects rods.

In the RPGRIP1 gene therapy study, cone function was significantly rescued in the canines while rod function was preserved. The therapy’s effect on vision persisted for 24 months — the length of time vision was monitored by the INSERM team.

Certain mutations in RPGRIP1 can also cause Leber congenital amaurosis (LCA), a severe form of retinitis pigmentosa that affects young children. Dr. Rolling says that her team’s gene therapy will target LCA caused by RPGRIP1 mutations.

A Foundation-funded research group from Massachusetts Eye and Ear Infirmary (MEEI) is also developing a gene therapy for LCA caused by mutations in RPGRIP1. Their lab studies are ongoing as they move toward launching a clinical trial.

“We are very pleased with the RPGRIP1 gene therapy efforts at INSERM and Mass Eye and Ear,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “As these two teams report results, they will learn from each other. Ultimately, that will help lead to an optimal therapy for the patients.”

Both the MEEI and INSERM treatments involve delivery of healthy copies of the RPGRIP1 gene to replace defective copies. The researchers insert the healthy copies into a specially designed virus which penetrates rods and cones to deliver the therapeutic genetic cargo. The virus is contained in a drop of liquid injected underneath or near the retina. Studies have shown that a single administration of gene therapy can last several years, perhaps a lifetime.

The virus used for the studies is known as an adeno-associated virus, or AAV. It is similar to the AAV being used in landmark clinical trials of LCA (RPE65 mutations) gene therapy at the Children’s Hospital of Philadelphia, the Universities of Pennsylvania and Florida and other research centers. The AAV is widely used because it penetrates cells of the retina well and has a good safety profile in humans.