Gene therapy transforms eyesight of 12 born with rare defect


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, an achievement that was hailed as a major accomplishment for gene therapy. They have now treated an additional nine patients, including five children, and find that the best results are 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, had immense difficulties in navigating an obstacle course and required special enlarging equipment for books and help in the classroom.


Today, after a single injection of a gene-therapy product in one eye, he rides his bike around the neighborhood, needs no assistance in the classroom, navigates the obstacle course quickly and has even played his first game of softball.

The results are “astounding,” said Stephen Rose, chief scientific officer of Foundation Fighting Blindness, which supported the work but was not involved directly. “The big take-home message from this is that every individual in the group had improvement . . . and there were no safety issues at all.”

The study “holds great promise for the future” and “is appealing because of its simplicity,” wrote researchers from the Nijmegen Medical Center in the Netherlands in an editorial accompanying the report, which was published online Saturday by the journal Lancet.

The 12 patients had Leber’s congenital amaurosis, which affects about 3,000 people in the United States and perhaps 130,000 worldwide. Victims are born with severely impaired vision that deteriorates until they are totally 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. Mistakes in 13 different genes are known to cause it, but all 12 of the patients suffered a defect in a gene called RPE65. This gene produces a vitamin A derivative that is crucial for detecting light.

About five children are born each year in the United States with that 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 A. High, Dr. Albert M. 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.

Maguire used a long, thin needle to insert the preparation into the retina of the worst eye in each of the patients. Within two weeks, the treated eyes began to become more sensitive to light, and within a few more weeks, vision began to improve. The younger the patients were, the better they responded. That was expected, Bennett said, because similar results had been observed in dogs and rodents.

By both objective and subjective measures, vision improved for all the patients. They were able to navigate obstacle courses, read eye charts and perform most of the 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.

Bennett noted that the oldest patient in the trial, a mother, had not been able to walk down the street to meet her children at school. “Now she can. She also achieved her primary goal, which was to see her daughter hit a home run.”

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 have not optimized the dosage of the adenovirus used to carry the gene into the eye. Those issues will be studied in Phase 2, a larger clinical trial that they hope to begin soon.

Meanwhile, the team has begun treating some patients at the University of Iowa.

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.