Results from a first-of-its-kind clinical trial show that a gene therapy treatment improves vision and function for blind children and adults and suggests the approach could be on its way to becoming the first-ever gene therapy to be approved by the Food and Drug Administration (FDA).
Stephen Russell, MD, is the lead author of a team of researchers from the UI. He is clinical director for the Carver Family Center for Macular Degeneration in the Stephen A. Wynn Institute for Vision Research and Schrage Professor for Macular Degeneration Research at the UI Carver College of Medicine. His team is working with Jean Bennett, MD, PhD, and Albert Maguire, MD, from the University of Pennsylvania, along with researchers from Children’s Hospital of Philadelphia, and Spark Therapeutics, in creating a gene therapy that treats certain rare, inherited eye disorders that cause blindness. Patients involved in the clinical trial have maintained improved vision for more than a year.
The study was published in The Lancet.
The gene therapy targets Leber’s congenital amaurosis (LCA), a retinal disease caused by mutations in the gene RPE65.
In the study, 29 patients between the ages of 4 and 44—none of whom could see well enough to walk unassisted in a regularly lit room—were given the gene therapy developed by Spark Therapeutics, Inc., and tested on their ability to navigate a room set up as a kind of obstacle course.
The treatment, SPK-RPE65, is injected directly into the eye. In the final stage of the trial, patients were directed by arrows through a mobility course in seven different light levels. The course changed with each change of light level. The lowest level of light was that of a moonless summer night, and the brightest was that of a well-lit office.
“These are kids who could not walk through a room in normal light, and who were absolutely paralyzed in dim light,” Russell says. “Now they’re walking around markedly better.”
After a year, patients treated in both eyes improved by 1.9 light levels, and their visual acuity improved by eight letters, roughly one and a half lines on an eye chart, Russell says.
Russell says the outlook for this new gene therapy is promising.
“First, it is the first Phase 3 trial completed for a gene therapy treatment. Since a Phase 3 trial is the last scientific step prior to FDA approval, this gene therapy treatment will likely become the first FDA-approved gene therapy for any condition,” he says. “Second, this trial met the clinical and FDA endpoints of improvement. Most gene therapies are intended to prevent further loss. This treatment demonstrated an improvement. In that way it is not typical for gene therapy, but given the checkered history of gene therapy this is a clear signal that this approach has value.”
Additionally, Russell says, while the condition tested in this trial is rare, about three-fourths of ocular diseases are caused by mutations in genes that can fit into the adeno-associated virus (AAV) that was used to deliver the SPK-RPE65 gene therapy. As AAV has proven to be safe for use in humans, this therapy could then represent “a plausible delivery system for other disorders.”
Other UI researchers involved in the study include Edwin Stone, MD, PhD; Jean Walshire; Taylor Keyhoe; Hannah Reichert; Maria Davis; Wanda Ffeifer; Elliot Sohn, MD; Vinit Mahajan, MD; Chris Johnson, PhD; Arlene Drack, MD; and Michelle Weckmann, MD.