Gene therapy transforms eyesight for 12

By Thomas H. Maugh II
Los Angeles Times

Pennsylvania researchers using gene therapy have made significant improvements in vision in 12 patients with a rare inherited visual defect, a finding that suggests it may be possible to produce similar improvements in a much larger number of patients with retinitis pigmentosa and macular degeneration.

The team last year reported success with three adult patients. They have now treated an additional nine patients, including five children. The best results were achieved in the youngest patients, whose defective retinal cells have not had time to die off.

The youngest patient, 9-year-old Corey Haas, was considered legally blind before the treatment began. He was confined largely to his house and driveway when playing and had immense difficulties in navigating an obstacle course.

Today, after a single injection of a gene-therapy product in one eye, he rides his bike around his neighborhood, navigates the obstacle course quickly and has even played his first game of softball.

The results are "astounding," said Stephen Rose, at the Foundation Fighting Blindness, which supported the study. "Every individual had improvement ... and there were no safety issues at all."

The study was published online Saturday by the journal Lancet. The 12 patients suffered from Leber's congenital amaurosis, which affects about 3,000 people in the U.S. Victims are born with severely impaired vision that deteriorates until they are blind, usually in childhood or adolescence. There is no treatment.
Leber's is a good candidate for gene therapy because most of the visual apparatus is intact, particularly at birth and in childhood. All 12 of the patients suffered a defect in a gene called RPE65 that produces a vitamin A derivative crucial for detecting light.

That specific defect, which was chosen because researchers at the Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine had cloned the gene, making copies available for use.

The study, led by Dr. Katherine High, Dr. Albert Maguire and Dr. Jean Bennett of those two institutions, enrolled five people in the United States, five from Italy and two from Belgium. Five were children, and the oldest was 44.

The good copy of the RPE65 gene was inserted into a defanged version of a human adenovirus.

The engineered virus then invaded retinal cells and inserted the gene into the cells' DNA.

All the patients' vision improved. They were able to navigate obstacle courses, read eye charts and perform most tasks of daily living. The improvement has now persisted for as long as two years.

The children who were treated "are now able to walk and play just like any normally sighted child," Maguire said.

There are clear limitations to the study. The patients' vision was not corrected to normal because of the damage that had already been done to the retina, and only one eye was treated.

"The big elephant in the room is: Can you treat the other eye?" Rose said. The foundation will put more funding into the research "to make sure that if you go back and treat the other eye, it won't ablate the positive results in the first eye due to an immune reaction or something else."

Researchers also hope they will be able to translate the results to other congenital conditions using different genes. Leber's is one form of retinitis pigmentosa, which affects an estimated 100,000 Americans.

The findings might be applicable to macular degeneration, which affects an estimated 1.25 million Americans and is the major cause of visual impairment in the elderly.

For more information go to www.maculardegenerationassociation.org