Gene therapy successful on blindness

Corey Haas used to need a high schooler to accompany him on the soccer field, to point out where the ball was.

Whenever the 9-year-old played with his Lego blocks, he had to feel around for them. At school in Upstate New York, he needed the help of a teacher's aide and a special computer screen to display class materials in giant size.

Not anymore.

A year and a half after reporting that they could restore some vision to young adults with a rare form of blindness, a team of Philadelphia researchers announced today that their gene therapy technique works even better in children.

Twelve patients, the oldest one age 44, received an injection of corrective genes in one eye to replace the malfunctioning genes they were born with. Corey, the youngest of the 12 when he was treated last year at age 8, saw some of the biggest improvement.

His treated eye became 10,000 times more sensitive to light, as measured by the pupil's ability to constrict, said the University of Pennsylvania's Jean Bennett, senior author of the findings published in The Lancet. The eyes of the adults became hundreds of times more sensitive, at best.

All 12 experienced at least some visual gains in the trial, done in collaboration with Children's Hospital of Philadelphia. None is close to having normal eyesight. But depending on how the term is defined, several, including Corey, are no longer classified as legally blind.

The results mark one of the few successes thus far in the young field of gene therapy, though the pace is starting to accelerate. Two other teams of researchers, one of them led by Penn's Samuel G. Jacobson, have reported improvements in patients with the same form of blindness - Leber's congenital amaurosis. Elsewhere, physicians have had some success in alleviating symptoms of Parkinson's disease by injecting genes into the brain.

Still others are removing defective bone-marrow cells, adding new genes, and reinserting the cells in order to tackle an inherited form of immune deficiency.

For various reasons, treating genetic defects that affect other parts of the body will be even more challenging, said Michel Sadelain, director of the Center for Cell Engineering at Memorial Sloan-Kettering Cancer Center in New York. Still, the new eye study is promising, he said.

"The results are superb," said Sadelain, who was not involved with the study. "This is extremely encouraging for the field in general."

Corey's parents first had a clue that the therapy was working just three or four days after the surgery, performed by Bennett's husband, Albert Maguire. On a sunny day at the zoo, the boy suddenly said that it was too bright, recalled his mother, Nancy.

At a news conference at Children's Hospital Thursday, she began to cry as she said that in the old days, "He never said that. Wow."

Corey now rides his bike in the street near the family's home in Hadley, N.Y., and he can see well enough to hit underhanded pitches in Little League baseball, said his father, Ethan. Before the surgery, they thought baseball was too dangerous for a boy who could barely see the ball.

"I'd be scared of having to go see the dentist," Corey's father said.

Corey is able to see colors better, so much so that on one occasion, he mistakenly thought one of his playmates had started to dye her hair a brighter hue. Unlike some of the 12 patients, Corey's ability to read letters on an eye chart did not improve. But he was already among the best of the bunch at that task, scoring about 20 over 200.

The reason children experienced greater improvements in light sensitivity is because Leber's congenital amaurosis is a progressive disease, said Stephen M. Rose, chief research officer at the nonprofit Foundation Fighting Blindness, which helped fund the study.

Patients' retinal cells deteriorate more as they get older, so younger people have more viable cells to rescue, he said. That's why the Penn-Children's trial was initially limited to those aged 27 and under; expectations for patients in their 20s were low.

But even those patients, including a pair of 26-year-old twins from Italy, improved more than the researchers expected. So the team expanded the trial to include a 35-year-old and a 44-year-old, who experienced modest improvement.

People who have the disease have a mutation in a specific gene, a flawed recipe that prevents their bodies from making a protein essential for converting light signals into something the brain can recognize.

The trial, which cost more than $2 million, has been more than a decade in the making. The surgery was tried first on dogs with the same kind of mutation. The first such dog, Lancelot, retains his improved vision more than nine years later.

But trying the technique on people was an even bigger step, said Katherine A. High, director of the Center for Cellular and Molecular Therapeutics at Children's Hospital - the study's primary funder. It required layers of government and university scrutiny, and the efforts of dozens of researchers.

"There's no training manual," said High, co-first author of the study.

Always in the back of the mind of any gene therapist is the early tragedy of Jesse Gelsinger, in 1999 at Penn. Gelsinger was injected with viruses that carried therapeutic genes, but he died when the microbes made his immune system go haywire. In the blindness trial, on the other hand, the genes are delivered by a primitive virus that can't make copies of itself.

Additional testing of the blindness treatment will follow, and High is hopeful that someday the team will get permission to treat children as young as age 3. Meanwhile, researchers intend to use similar genetic techniques to fight other inherited forms of blindness. Some are starting to explore ways to address the most common: macular degeneration.

In a few years, the Penn-Children's team hopes to seek government approval for their therapy used on Leber's. Eventually, the original 12 patients might have their other eye treated if the therapy wins additional approvals.

Corey's father said he would be eager to bring the boy back for that. In the meantime, Ethan Haas said he has to keep his own eyes on the active youngster.

Once reluctant to play outside, Corey now loves it, his father said.

"Now, it's getting really dark out and it's like, 'Gee, where's Corey?' "

Contact staff writer Tom Avril at 215-854-2430 or tavril@phillynews.com.