Results from Universities of Pennsylvania and Florida Study Reaffirm LCA Gene Therapy Potential

Three young adults with Leber congenital amaurosis (LCA) receiving gene therapy in a Phase I clinical study at the University of Florida and University of Pennsylvania demonstrated improved vision in brightly and dimly lit settings. The gene therapy was also shown to be safe for all three participants, who were ages 21-24.

Initial results of the study were published today in an online edition of the journal Human Gene Therapy. Additional findings from the study will be published shortly in the Proceedings of the National Academy of Sciences.

The LCA gene therapy under investigation at the Universities of Pennsylvania and Florida is similar to the LCA gene therapies in Phase I clinical studies at The Children’s Hospital of Philadelphia (CHOP) and Moorfields Eye Hospital in London. Results from those FFB-funded studies were published in the New England Journal of Medicine last April. All three participants in the CHOP trial reported improved visual acuity and better vision in dimly lit settings. One of three participants in the Moorfields study showed improved vision, as well.

“We are very pleased with the initially reported results of the LCA study at the University of Pennsylvania and University of Florida,” says Stephen Rose, Ph.D., Chief Research Officer, Foundation Fighting Blindness. “Of course, we are delighted to see some improvement in vision. However, the main objective in all these Phase I studies is to demonstrate safety, and they are doing just that. With safety established, we can move the treatments into more people and younger people. And we hope to see even more dramatic improvements in vision as the studies advance.”

In all three studies, the participants have a form of LCA that is caused by variations in the gene RPE65. LCA is a severe form of retinitis pigmentosa that causes blindness or severe vision loss in young children. Thus far, 12 different genes have been linked to LCA.

Though the treatments in the three studies are similar, there are some differences in the location and amount of gene therapy vector injected under the retina, as well as the promoter used to activate the gene. Promoters control gene “expression” — the amount of protein that the gene instructs retinal cells to make. Researchers want to identify a promoter that will lead to just the right amount of produced protein — not too much and not too little.

“We will learn different and complementary things from each of the three studies, and ultimately, researchers will be able to develop a better treatment using information from all of these clinical trials,” says Dr. Rose. “The bottom line is that multiple studies should lead to a more optimal treatment, and ultimately, a better opportunity to save and restore vision for patients. Also, continued success in these LCA studies will pave the way for developing gene therapy to treat other forms of retinitis pigmentosa, Usher syndrome, Stargardt disease, choroideremia, retinoschisis, and a variety of other retinal degenerative conditions.”

This University of Pennsylvania-University of Florida clinical study is being funded by the National Eye Institute. The Foundation Fighting Blindness funded much of the preclinical work that made this clinical effort possible.

Samuel G. Jacobson, M.D., Ph.D., of the University of Pennsylvania, is the study's principal investigator. Shalesh Kaushal, M.D., Ph.D., of the University of Florida, is the study’s lead surgeon. William Hauswirth, Ph.D., of the University of Florida, is the lead developer of the gene therapy.

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