First step to cure for blindness?
Gene therapy improved sight in 4 patients, study says
Some vision was restored in four of the six young people who got the treatment, teams of researchers in the United States and Britain reported yesterday. Two of the volunteers who could see only hand motions were able to read a few lines of an eye chart within weeks.
"It's a phenomenal breakthrough," said Stephen Rose, chief research officer of the Foundation Fighting Blindness, which helped pay for one study done at Children's Hospital of Philadelphia.
"I think this is incredibly exciting," said Dr. Jean Bennett, professor of ophthalmology at the University of Pennsylvania and a leader of the Philadelphia study. "It's the beginning of a whole new phase of studies."
The research was published online yesterday by the New England Journal of Medicine in conjunction with presentations at a medical meeting in Florida.
The two teams of scientists, working separately, each tested gene replacement therapy in three patients with a form of a rare hereditary eye disease called Leber's congenital amaurosis. There's no treatment for the disease, which appears early in infancy and causes severe vision loss, especially at night.
An estimated 2,000 Americans have the form of the disease they targeted, Bennett said.
Gene therapy - replacing faulty genes with a normal version - has been studied in humans for over 15 years with limited success. The field suffered a setback with the 1999 death of Jesse Gelsinger, 18, in an experiment for a liver disorder at Penn. And some children treated for an immune disorder called the "bubble boy disease" later developed leukemia.
Each of the participants in the eye experiments had mutations in a gene that makes a protein needed by the retina, which senses light and sends images to the brain. Those without the gene gradually lose sight until they are blind in early adulthood.
The retina itself stays in relatively good shape for a while, making it a good candidate for gene therapy, said Robin Ali, a professor at University College London, who led the British team. He likened the defective gene to a missing spark plug in a car engine.
"The whole engine can be absolutely fine, but if it doesn't have a spark plug, the car's not going to work," said Ali.
For the experiment, the scientists injected millions of copies of a working gene beneath the retina in the back of the eye. Only one eye was treated - the worst one - in case anything went wrong; the untreated eye was used for comparison. After the treatment, their eyesight and light sensitivity were measured periodically; mobility was tested in a maze or an obstacle course.
All three of those treated in Philadelphia showed significant improvement, the researchers said. The volunteers - two women, 19 and 26, and a man, 26 - were from Italy, where they had been screened by researchers. The longest follow-up was six months.
Besides reading lines on an eye chart, they could see better in dim light, Bennett said.
"We were not expecting to restore their vision to 20/20," she said.
In the British group, the treatment only worked in 18-year-old Steven Howarth, whose disease was less advanced than the other two - a girl, 17; and a man, 23, who was followed for a year.
The research in Philadelphia and London was paid for by a variety of government agencies and private foundations. Four of the Philadelphia researchers, including Bennett, have either applied for or have patents related to gene therapy. Ali and another British researcher have also applied for a patent for the procedure. *

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