In a first-of-its-kind procedure in New England, clinical researchers at UMass Medical School have used a gene therapy technique to introduce a normal-functioning gene into the eye of a patient with type 2 Leber Congenital Amaurosis (LCA), a rare, inherited eye disease that causes severe visual loss within the first few months of life.
A degenerative disease, LCA is caused by a group of recessively inherited genetic mutations that lead to an inability to make a light-sensitive protein in the retina. One of the most common gene mutations known to cause LCA occurs on the RPE65 gene according to Shalesh Kaushal, MD, PhD, principal investigator of the study and chair and associate professor of ophthalmology. “The RPE65 gene produces a protein that helps process vitamin A in the cells that nourish the retina. Because of the mutation, patients with type 2 LCA don’t process enough vitamin A, which is important for allowing the visual proteins that detect light to sense light.”
The Phase I/II trial will evaluate the safety of using a recombinant adeno-associated virus (AAV) vector to deliver a normal-functioning RPE65 gene to retina cells of patients with type 2 LCA. A small virus that occurs in humans, AAV does not cause any known pathology and creates only a mild immune response in its host. A fluid containing the AAV vector loaded with the normal RPE65 gene is introduced into the eye. As the fluid is absorbed by the eye, the virus, along with the normal RPE65 gene, attaches itself to the retina cells.
"Though this trial is being done specifically to study the safety of the delivery system, the eventual hope is that this will have the therapeutic effect of increased RPE65 protein delivery by retina cells and an improvement in vision,” said Dr. Kaushal.
An expert in vitreoretinal disorders, Kaushal joined UMMS in January from the University of Florida, where he was director of vitreoretinal services. He is one of the first researchers in the United States to use gene therapy to treat LCA. At Florida, he and Terence R. Flotte, MD, dean, provost and executive deputy chancellor, collaborated on earlier preclinical and phase I clinical trials for this disorder. “This trial marks a new era of translational medicine at the Medical School,” said Dr. Flotte. “The field of gene therapy holds tremendous promise for a great many diseases, and we are quite excited to contribute to the field with the extensive biomedical and clinical research acumen of our physician-scientists. Patients across the country are eagerly awaiting the day when they can benefit from the fruits of these trials.”