Emerging Recessive RP Gene Therapy Moves Closer to Human Study
August 9, 2012 – French researchers successfully used gene therapy to preserve vision in a canine model of autosomal recessive retinitis pigmentosa (arRP) caused by defects in the gene PDE6β. The advancement is a critical step forward in launching a clinical trial of the treatment for people with same form of arRP.
Results of the PDE6β gene therapy study were published on July 24, 2012, in the online edition of the journal Molecular Therapy.
In both people and animals, defects in PDE6β initially lead to loss of rods, the cells in the retina that provide peripheral vision and the ability to see in dark settings. But over time, degeneration in rods leads to loss of cones, the retinal cells that provide central and daytime vision. By treating rods with the PDE6β gene therapy, researchers hope to prevent vision loss entirely.
In their recent study, researchers injected a small drop of liquid containing the treatment underneath the retinas of the affected canines. The therapy consisted of healthy copies of PDE6β, which were inserted into a human-engineered adeno-associated virus, or AAV. The AAV penetrates retinal cells to deliver copies of the therapeutic PDE6β gene. AAVs are the gene delivery technology now being used in clinical trials of gene therapies for Leber congenital amaurosis (RPE65 defects), arRP (MERTK defects) and wet age-related macular degeneration.
Both behavioral and retinal sensitivity tests showed that the PDE6β gene therapy preserved vision for 18 months in canine eyes. The investigators note that the treated animals need to be monitored for a longer period of time to verify the therapy’s suitability for humans.
Dr. Fabienne Rolling, the study’s lead investigator from INSERM, a government-based research institution in Nantes, France, says that she and her colleagues are beginning to plan the process for identifying patients who may be suitable for a future clinical trial.
“This is very exciting work,” says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. “Demonstrating safety and effectiveness in a large animal model positions this team well for a clinical trial.”
