POSTED 8 MAY 2008
Gene therapy: success at last
In late April, researchers announced that they had slipped genes into the eyes of six blind people, and improved the vision in four -- with almost no dangerous side effects. These extremely limited reports were a rare victory for gene therapy: medical treatments that substitute working genes for broken genes.
Theoretically, gene therapy could treat most diseases with roots in gene problems, but techniques that worked in animals failed in people. Treatments that looked like a slam dunk ended up being anything but. And some patients died along the way.
In retrospect, the initial hope (or was it hype?) looks naïve. Squirting in genes so they work in the right place, at the right rate and (only) at the right time, is fiendishly complicated. Ditto for avoiding immune attack on the viruses that carry the genes, the genes themselves or the proteins that the genes make.
But now, two promising reports on the same blinding disease give a struggling field sorely needed encouragement.
University of Pennsylvania
Most significant was the improvement in all three patients in a trial at the University of Pennsylvania. "We found very strong evidence for recovery of some visual function, from subjective and objective data," says Jean Bennett, professor of ophthalmology at Penn's Scheie Eye Institute. "The patients reported improvements, starting at 10 days to two weeks after the injection, and the improvements continued to grow. They would call and e-mail, saying, 'Today I can read two more lines on the eye chart,' or 'I can see a snow-capped mountain' or 'I can read the numbers on license plates.'"
A checkered history
Advances in genetics during the past 50 years encouraged a mechanistic view of the body: If a defect in Gene X causes Disease Y, simply insert a good copy of Gene X, and you have cured Disease Y.
The reality, though, has not been simple, and gene therapy has struggled with setbacks:
- In 1999, a teenager named Jesse Gelsinger died, apparently from a monster immune reaction, four days after an injection of virus-carrying genes to treat his severe liver disease. The Food and Drug Administration disciplined Gelsinger's doctor for various mistakes.
- A successful gene treatment for severe combined immunodeficiency (SCID) was announced in 2000. SCID patients (most famously, the "bubble boy") have almost no defense against infection, and most die very young. By now, four of 27 SCID patients who received new genes have developed leukemia, because the inserted genes destabilized their chromosomes. (To be fair, SCID is probably more deadly than childhood leukemia, but cures are not supposed to cause cancer.)
- In July 2007, a woman died following gene therapy for rheumatoid arthritis; investigators exonerated the treatment, from a company called Targeted Genetics, and the trial will resume.
These setbacks may be inevitable when the treatment affects the labyrinthine interaction of genes and the body. But if genes play such critical roles in so many diseases, why is gene therapy so feckless? And aside from the troubled treatment for SCID, where are the cures?
Now we hear that gene therapy has brought eyesight to the blind! Let's take a peek ...
Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive