Gene Therapy Improves Vision in Patients with Congenital Retinal Disease

In a clinical trial at The Children’s Hospital of Philadelphia, researchers from The University of Pennsylvania have used gene therapy to safely restore vision in three young adults with a rare form of congenital blindness. Although the patients have not achieved normal eyesight, the preliminary results set the stage for further studies of an innovative treatment for this and possibly other retinal diseases.

An international team led by The University of Pennsylvania, The Children’s Hospital of Philadelphia, the Second University of Naples and the Telethon Institute of Genetics and Medicine (both in Italy), and several other American institutions reported their findings today in an online article in the New England Journal of Medicine.

“This is the first gene therapy trial for a nonlethal pediatric condition,” said Albert M. Maguire, M.D., Associate Professor, Department of Ophthalmology, University of Pennsylvania School of Medicine and a physician at The Children’s Hospital of Philadelphia. Maguire, together with his wife, Jean Bennett, M.D., Ph.D., Professor of Ophthalmology at Penn and Senior Investigator at the F.M. Kirby Center for Molecular Ophthalmology at Penn’s Scheie Eye Institute, have been researching inherited retinal degenerations such as Leber congenital amaurosis (LCA), for 18 years. LCA is a group of inherited blinding diseases that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness during a patient’s twenties or thirties. Currently, there is no treatment for LCA.

“Patients’ vision improved from detecting hand movements to reading lines on an eye chart,” Maguire added. In 2001, Bennett and Maguire were part of a team which reported successfully reversing blindness using gene therapy on dogs affected by the same naturally occurring form of congenital blindness.

The current study is sponsored by the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia, directed by Katherine A. High, M.D. High, a study leader and an Investigator of the Howard Hughes Medical Institute, has been a pioneer in translational and clinical studies of gene therapy for genetic disease, and in 2005 initiated a collaboration with Bennett and her group to translate their exciting animal findings into a clinical study.

The scientists used a vector, a genetically engineered adeno-associated virus, to carry a normal version of the gene, called RPE65, that is mutated in one form of LCA. Three patients, ages 19, 26 and 26, received the gene therapy via a surgical procedure performed by Maguire between October 2007 and January 2008 at The Children’s Hospital of Philadelphia, where the gene vector was manufactured at the hospital’s Center for Cellular and Molecular Therapeutics (CCMT).

Starting two weeks after the injections, all three patients reported improved vision in the injected eye. “Standard vision tests showed significantly improved vision in the patients,” said Alberto Auricchio, M.D., a study leader from the Telethon Institute of Genetics and Medicine and University of Naples Federico II. The researchers also reported that each injected eye became approximately three times more sensitive to light, and each was improved compared to the uninjected, previously better functioning eye.