Leber congenital amaurosis (LCA) is a group of inherited diseases that damage the light receptors in the retinas of affected individuals. LCA, which affects approximately 1 in 80,000 people, is progressive. Patients usually begin to lose their sight early in childhood and become completely blind in their twenties or thirties.

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, and 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 degeneration syndromes such as Leber congenital amaurosis (LCA), for the last two-plus decades.

LCA is caused by mutations in a single gene, called RPE65. Without functioning RPE65protein, light-sensitive photoreceptor cells are starved of a retina-specific form of vitamin A and cannot function, blocking vision. In 2008, Maguire and Bennet reported that they had successfully restored partial vision in one eye of each of three young adult patients by transferring a functional copy of the RPE65 gene into the subretinal space in the treated eye of each patient. One year later the researchers reported that the visual gains the patients had experienced in the first few weeks after treatment were still present.

Based on those early promising results, the investigators expanded the clinical trial to include five children and seven more adults with LCA. The greatest improvements occurred in the children, all of whom were able to navigate a low-light obstacle course after treatment.

Although the results are already life-changing for LCA patients and their families, the researchers continue working to improve the therapy. Because animals treated with a second round of therapy in the previously untreated eye, suffered no adverse immune responses, LCA patients in the original trial are now getting their other eye treated and another trial is in Phase III.

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