Press Releases

FDA advises that gene therapy trials go forward for bubble boy disease

By Lauran Neergaard
Friday October 11, 2002


GAITHERSBURG, Md. — Gene therapy that seems to cure an often fatal immune disorder also likely gave a French toddler a leukemia-like illness, but U.S. scientists want the genetic experiments restarted anyway — calling the risk too low to deprive desperate children of treatment. 

The Food and Drug Administration called an emergency meeting of its scientific advisers Thursday to decide whether three U.S. gene therapy experiments recently suspended because of the French boy’s illness should resume. France also suspended the experiment. 

The disorder often known as “bubble boy disease” — formally called severe combined immunodeficiency, or SCID — is the only disease where gene therapy has ever worked. 

The toddler is the first recipient of gene therapy for any disease to suffer a cancerous side effect. But scientists have long warned that cancer is a possible risk if the virus used to deliver new genes into a patient’s body slips into the wrong place. 

The evidence “is pretty convincing” that now that has happened, said Dr. Philip Noguchi of the Food and Drug Administration, after French researchers showed evidence the virus they used affected a cancer-promoting gene in the boy’s body more than a year after it cured his SCID. 

It took another year and a half before the boy developed leukemia-like symptoms. Chemotherapy appears to be working, and tests soon should tell if the 3-year-old is in remission, Paris’ Dr. Alain Fischer told the FDA meeting. 

Still, there is only one report of gene therapy-linked leukemia — while some popular chemotherapies carry a 10 percent risk that in curing today’s cancer the patient will get leukemia years later, cautioned Dr. Crystal Mackall of the National Cancer Institute. 

“You can be doing harm when you withhold a promising treatment,” added Dr. Joanne Kurtzberg of Duke University, echoing a woman who told the panel that the experiment is her 10-year-old grandson’s last hope. 

The FDA advisers ultimately recommended that gene therapy experiments be reopened to SCID patients who don’t have the option of a bone marrow transplant from a well-matched donor, today’s best treatment. The FDA usually follows its advisers’ recommendations. 

But some panelists worried that the leukemia finding’s implications go beyond SCID to every gene therapy experiment that ever used a retrovirus, a kind of virus that permanently invades cells. 

“We owe an extra measure of regard to all the people still alive who volunteered for gene therapy. They should be told about this risk and check for it,” said Abby Meyers of the National Organization for Rare Disorders. 

She angrily noted that eight years after Congress ordered the FDA to create a registry of gene recipients in case long-term side affects ever appear, the agency hasn’t done so. The FDA still is working to ensure survivors of all 150 retroviral gene therapy studies ever done are notified of the French case, Noguchi said. 

People signing up for future retroviral gene therapy for any disease must be more strongly warned that leukemia is a risk — with specific discussion of the French case, the advisers added. 

Babies with SCID 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 Fischer generated great excitement when his gene therapy apparently cured nine of the 11 children he treated, all with the most severe type of SCID-type, called X-SCID, that afflicts only boys. 

Similar U.S. studies poised to begin have been put on hold. 

Fischer took bone marrow from the boys and culled from it skin cells that are supposed to create blood cells. He mixed in a retrovirus containing the immune-creating gene their bodies lacked, and reinjected the stem cells, which in nine boys started working properly. 

Intricate molecular studies of the toddler who got the leukemia-like illness three years after his gene therapy found the virus that delivered the SCID-curing gene also inserted itself into numerous other spots on cells, including a leukemia-promoting gene. 

That alone likely wasn’t enough to sicken him, several scientists said, but may have been the final piece of bad luck on top of a family predisposition to cancer and other still unknown factors.