U.S. Suspends 27 Gene Therapy Trials

U.S. officials are suspending 27 more gene therapy studies while they investigate a possible serious risk: A second European toddler cured of the deadly "bubble boy disease" by gene therapy has come down with an apparent leukemia-like side effect.

It marks the second time in three months that health officials have interrupted gene therapy studies because of the grave side effect.

Bubble boy disease — an immune disorder formally called severe combined immunodeficiency, or SCID — is the only disease ever to be cured with gene therapy. But three months ago, a boy whose life was saved by a SCID gene therapy experiment in France when he was a baby came down with a leukemia-like syndrome at age 3.

Scientists have long warned that cancer is a possible risk from any gene therapy, such as that for SCID, that uses retroviruses, a type of virus that permanently invades cells, to deliver new genes into a patient's body. Still, no one given gene therapy for SCID or other diseases had ever had such a side effect.

That first sick toddler prompted U.S. and French scientists in October to stop gene therapy experiments for SCID, including three in this country.

Now a second child in the French SCID experiment has come down with that same leukemia-like side effect, Food and Drug Administration scientists announced.

Quietly notified by French researchers about a month ago, the FDA decided that the second serious side effect warranted the more serious response: temporarily stopping about 27 more U.S. experiments that use retroviruses to insert new genes into blood stem cells in hopes of fighting diseases other than SCID.

The FDA didn't release a list of the experiments but said they include some targeting such diseases as cancer and include several hundred participants.

The FDA said if researchers argue that any of the retrovirus experiments offered a sole option to people with life-threatening illnesses, the agency would work to let them restart on a case-by-case basis, with appropriate warnings to participants.

The three SCID gene therapy experiments, however, remain on hold for at least a few more months while officials investigate the second side effect, FDA officials said.

"We do think it's a prudent course," because "there are things going on here that we really don't understand," FDA gene therapy chief Dr. Phil Noguchi said.

The FDA will convene its scientific advisers next month to pore over the research and debate future steps.

"It's very unfortunate that with the first real success in a very difficult disease, that there's this downside," said American Society for Gene Therapy president Joe Glorioso, a University of Pittsburgh geneticist.

Without the gene therapy, these two boys almost certainly would have died of their SCID because they had no other treatment options, he noted. Yet without the gene therapy, he said, "it's unlikely these patients would have ever developed leukemia."

Both boys responded well to chemotherapy and are stable, but their long-term outlook is uncertain, Noguchi said. He released few details about the second patient, including his nationality, other than that he was cured of SCID as a baby and became ill with the cancer-like syndrome almost three years later.

SCID babies are born without the ability to produce disease-fighting immune cells. The best known victim was David, Houston's famous "bubble boy" who lived in a germ-proof enclosure until his death at age 12 in 1984.

There are some SCID treatments, including bone marrow transplants that can allow patients to live normal lives. But transplant success varies widely, and many children still die young.

So Paris' Dr. Alain Fischer generated great excitement when his gene therapy apparently cured nine of the 11 boys he treated who had the most severe SCID-type, called X-SCID. He drew bone marrow from the boys, culled immune cell-creating stem cells from it, and mixed in a virus containing the gene their bodies lacked. Injected back into their bodies, the stem cells worked properly.