Gene therapy may aid blind

For the first time, researchers have used gene therapy to improve vision in patients who were virtually blind, offering new hope to hundreds of thousands with inherited forms of vision impairment.

The research, some of which involves Seattle biotech Targeted Genetics, marks a major milestone for gene therapy, a discipline many scientists find promising but that so far has failed to produce a marketable product in the U.S.

It also casts a positive light on the Seattle company, a gene-therapy research firm that was shaken last July by the death of an Illinois woman enrolled in its lead drug candidate's clinical trial. Federal investigators eventually determined gene therapy was not the culprit and allowed the trial to resume.

Although the six patients studied have an extremely rare form of blindness called Leber's congenital amaurosis, researchers believe the approach ultimately could be used for a broader spectrum of disorders, including retinitis pigmentosa and macular degeneration.

"It's a landmark"

"In the field of retinal dystrophies, this is, I believe, the most important therapeutic discovery" in four decades, said Dr. Morton Goldberg, an ophthalmologist at John Hopkins University's Wilmer Eye Institute. "It's a landmark."

The rarity of the disease could also help propel the launch of a commercial product by the Seattle company, as so-called orphan drugs — designed to treat diseases that affect relatively few — get preferential treatment with regulators.

"We're making plans and evaluating that now," said Targeted Genetics Chief Executive H. Stewart Parker. If everything goes well, approval could come "as quickly as 18 months," she said.

The treatment, so far meant only to prove the safety of the technique, "made a real difference in patients' lives," said geneticist Robin Ali of University College London, the senior author of one of two reports presented Sunday at a Fort Lauderdale, Fla., meeting of the Association for Research in Vision and Ophthalmology. Targeted Genetics worked with the British researchers.

The reports were published online Sunday by the New England Journal of Medicine.

The results are particularly important because gene therapy, in which a good gene is substituted for a naturally occurring defective one, has been "a snakebitten field," with at least two subjects in other experiments dying and a handful of others developing cancer, said Dr. Albert Maguire of the University of Pennsylvania School of Medicine, lead author of the second report.

While cataract surgery and medication can restore sight in patients with other eye ailments, doctors had not been able to restore vision to patients with this kind of hereditary degenerative disease, Maguire said.

Leber's congenital amaurosis affects about 3,000 people in the United States and perhaps 1 in every 50,000 worldwide. Children with the disorder are born with severely impaired vision that deteriorates over the course of their lives until they are totally blind. There is no treatment.

What makes Leber's a good candidate for gene therapy is that most of the visual apparatus, including the retina, is intact — at least at birth. Typically, the defective gene is one of several in a biochemical pathway that produces chemicals necessary for the eye to generate an electrical signal for transmission to the brain.

If that gene could be replaced before the visual apparatus deteriorates from lack of use, vision could be restored, Maguire said.

Potential treatments

That same basic strategy could be used to treat a variety of congenital retinal disorders, said Dr. Katherine High of Children's Hospital of Philadelphia and a co-author of one of the studies.

Retinitis pigmentosa — the broad family of disorders that includes Leber's — affects an estimated 100,000 Americans. Macular degeneration affects 1.25 million Americans; the number is expected to grow to 3 million by 2020 as the population continues to age.

Those conditions are caused by other defective genes, but the treatment principle would be the same.

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 — in case anything went wrong; the untreated eye was used for comparison.

After the treatment, eyesight and light sensitivity were measured periodically; mobility was tested in a maze or an obstacle course.

The Pennsylvania group treated three patients, ages 19, 26 and 26, recruited by Dr. Alberto Auricchio of the University of Naples Federico II in Italy.

Beginning two weeks after treatment, all three patients reported improved vision, Maguire said. Light sensitivity improved about threefold, and the treatment reduced nystagmus, involuntary movement of the eye often seen in blind people. One patient's vision on an eye chart also improved.

In the British group, the treatment worked only 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 National Eye Institute is funding a third similar study at the University of Florida.

Seattle Times business reporter Ángel González provided information on Targeted Genetics. Information from The Associated Press and USA Today is included in this report