Gene Therapy in Ophthalmology Update 8: Promising Results in the Treatment of Leber’s Congenital Amaurosis (LCA)

As noted in the Gene Therapy in Ophthalmology by Application table shown in Update 7, there are seven clinical trials underway at various institutions aimed at the treatment of Leber’s Disease. Some of these trials have been underway for several years with multiple patients having been treated.

When I sent a copy of the table to Dr. Stephen Rose, chief research officer for the Foundation Fighting Blindness for comments and review, I also asked the question, “Who is tracking and reporting on the results of the patients already treated?” I didn’t get a direct response, but a few days later, the FFB reported the following story on its web site, providing some insight into the results being obtained.

Pennsylvania-Florida Team Reports Promising Three-Year Results for LCA Clinical Trial

Foundation Fighting Blindness

January 13, 2012 - Three years after it began, the landmark Phase I gene therapy clinical trial for people with Leber congenital amaurosis (LCA) at the Universities of Pennsylvania and Florida (NCT00481546) continues to go very well. Overall safety and vision improvements have been sustained. All 15 participants in the study, ranging in age from 11 to 30, have demonstrated vision improvement to varying degrees, including increases in visual field, night vision and mobility. Improvements in visual acuity only occurred in those who entered the trial with the lowest visual acuity.

"We are extremely pleased with the latest report coming from the Penn-Florida study. It is imperative that we demonstrate long-term safety and effectiveness of the treatment, and the team is doing that superbly," says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. "We are also impressed by the depth and scope of their analyses of the treatment, which not only validate their results, but will greatly increase the chances of success for future gene therapy clinical trials for LCA and other retinal diseases."

The University of Pennsylvania's Dr. Samuel Jacobson, lead investigator for the clinical trial, and Dr. Artur Cideciyan, his co-investigator, say their team has learned that targeting certain areas of the retina for injection of the treatment is critical to both safety and effectiveness. Specifically, injections underneath the fovea, the central area of the retina with the highest concentration of cones, didn't improve vision and could potentially lead to damage or detachment. They believe that a strategy of two or three injections at different points outside the fovea will be optimal for treating many of these LCA patients.

Dr. William Hauswirth, a Foundation-funded gene therapy development expert and trial co-investigator from the University of Florida, is conducting lab studies of a gene therapy injection approach that may reduce the overall risk of retinal damage and detachment. As a potentially safer alternative to subretinal injections, he is evaluating intravitreal injections made near the front of the retina. The challenge with the intravitreal approach is ensuring that the treatment, which is contained in a tiny drop of liquid, gets to the retinal cells that need it. Dr. Hauswirth notes that different injection sites and strategies might be warranted for different diseases.

In addition to the Universities of Pennsylvania and Florida study, four other clinical trials are underway for gene therapy for LCA caused by mutations in the RPE65 gene. Those studies are being conducted by: The Children's Hospital of Philadelphia (CHOP), Moorfields Eye Hospital in London, Hadassah Medical Organization in Jerusalem, and Oregon Health & Science University, for the company AGTC. The Foundation is funding the clinical trials at CHOP and Moorfields, and funded much of the preclinical work that made them all possible.

All of the gene therapies in these clinical trials use a manmade adeno-associated virus, or AAV, to deliver normal copies of the RPE65 gene to replace the mutated copies in the retina. More than 40 people have been treated in the five RPE65 gene therapy clinical trials.

For additional information about this study, also see Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations, published in the Archives of Ophthalmology, September 12, 2011.