Leber's congenital amaurosis sufferers could benefit from gene therapy trial

Mar 11, 2010

Last year a human trial involving administering gene therapy to Leber's congenital amaurosis (LCA) patients produced improvements in 12 children and young adults. The same researchers then conducted an animal study that found that a second injection into the previously untreated eye, was safe and effective with no signs of interference from immune reactions from the earlier injection.

Last year a human trial involving administering gene therapy to Leber's congenital amaurosis (LCA) patients produced improvements in 12 children and young adults. The same researchers then conducted an animal study that found that a second injection into the previously untreated eye, was safe and effective with no signs of interference from immune reactions from the earlier injection.

The new findings suggest that patients who benefit from gene therapy in one eye may experience similar benefits from treatment in the other eye LCA, a retinal disease that progresses to total blindness by adulthood.

Researchers had exercised caution by treating only one eye in the human trial. In the current study, the study team found no evidence of toxic side effects in the blood or the eyes of the 10 animals--six dogs and four monkeys--that received the gene therapy. Each animal received an injection first in the right eye, then in the left eye 14 days later. All six dogs, which had been specially bred to have congenital blindness, had improved vision, in addition to showing no toxic effects from the gene therapy.

“We designed this study to investigate the immunological consequences of administering the gene therapy injection to the second eye after treating the first one,” said corresponding author Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine. “The good news is that in animals, the second injection, like the first, is benign.”

As in the human trials of this gene therapy, the researchers packaged a normal version of the gene that is missing in LCA inside a genetically engineered vector, adeno-associated virus (AAV). The vector delivers the gene to cells in the retina, where the gene produces an enzyme that restores light receptors. Although the virus used does not cause human disease, it previously set off an immune response that cut short the initial benefits of gene therapy, notably in a 2002 human trial of gene therapy for the bleeding disorder haemophilia.

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