September 4, 2009

WORCESTER, Mass. – In a first-of-its-kind procedure in New England, clinical researchers at the University of Massachusetts Medical School (UMMS) 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 and inherited eye disease that causes severe visual loss within the first few months of life. The procedure was performed as part of a Phase I/II clinical trial to study the safety and efficacy of using a recombinant adeno-associated virus (AAV) vector to replace a faulty gene that prevents the production of protein crucial for sight. The trial is sponsored by Applied Genetic Technologies Corporation (AGTC) of Gainesville, FL.

“This trial marks a new era of translational medicine at the Medical School,” said Terence R. Flotte, MD, dean, provost, and executive deputy chancellor of UMMS. “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.”

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,” said Shalesh Kaushal, MD, PhD, principal investigator of the study and chair of ophthalmology at UMMS. “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 at UMMS will evaluate the safety of using a recombinant AAV vector to deliver a normal-functioning RPE65 gene to retina cells of patients with type 2 LCA. A small virus known to occur in humans, AAV does not cause any known pathology and creates only a mild immune response in its host. Once introduced into cells, AAV has the ability to leave its genome in the targeted cells, making it a potential therapeutic delivery system for transferring normal genes to patients suffering from certain genetic disorders.

In the LCA clinical trials performed at UMMS, a fluid containing the AAV 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,” said Kaushal. “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.”

Interestingly, said Dr. Kaushal the retina’s lack of an immune response works in its favor. “When a foreign substance is introduced into human tissues and cells, it triggers the body’s immune system,” said Kaushal. “Stimulation of the body’s immune system can inhibit the effectiveness of gene therapy treatments, and in some cases can have an adverse effect on the body and other healthy tissues. However, the retina lacks an immune mechanism, which makes treating eye diseases with gene therapy possible.”

An expert in vitreoretinal disorders, Dr. Kaushal joined UMMS in January from the University of Florida where he was assistant professor of ophthalmology and director of vitreoretinal services and is one of the first researchers in the United States to use gene therapy to treat LCA. At Florida, he and Flotte had collaborated on earlier preclinical and phase I clinical trials for this disorder.

Dr. Kaushal is a member of the Gene Therapy Center, part of the Advanced Therapeutics Cluster at UMMS. Established around the promise that lies within the application of the recombinant adeno-associated virus (rAAV), the Gene Therapy Center is performing translational research into Cystic Fibrosis, Alpha-1 Antitrypsin Deficiency, Lysosomal Storage Diseases, Canavan Disease, Retinal and Macular Degeneration and other genetic diseases.

Applied Genetic Technologies Corporation, a privately-held, clinical stage biotechnology company developing systems to deliver human therapeutics, is sponsoring the LCA clinical trials at UMMS. “We are delighted to be working with Dr. Kaushal and the University of Massachusetts Medical School on this research,” said Sue Washer, President and CEO of AGTC. “There are thousands of patients suffering from LCA who currently have no treatment options and this trial, which is evaluating larger doses than in a previous Phase I study, is another step towards using the AAV delivery system to address this disease and improve the patients’ quality of life.”

The Food and Drug Administration has yet to approve gene therapy treatments for any disease.

About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $200 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit

About Applied Genetic Technologies Corporation
AGTC is focused on the research and development of novel therapeutics for patients with unmet medical needs utilizing AGTC’s proprietary, non-pathogenic adeno-associated virus (AAV) delivery system. AGTC has demonstrated that this system can be used to deliver a normal form of a gene in both animals and humans thus allowing their own body to produce sustained therapeutic levels of important biologics. The Company’s most advanced programs in development are treatments for Alpha-1 antitrypsin deficiency, a disease causing a progressive loss of lung function, and Leber’s Congenital Amaurosis, an inherited condition causing early blindness. Both utilize AGTC’s proprietary AAV system and production methods. The Company is located near Gainesville, Florida and is financed by the nationally renowned venture firms InterWest Partners, Intersouth Partners, and MedImmune Ventures. For more information see