Originally created 04/28/00

Long-awaited gene therapy restores two babies to health

WASHINGTON -- In an exciting and long-awaited success, gene therapy has restored apparently normal immune systems to two French babies born with a rare, lethal immune disease sometimes called the "bubble boy disease."

It's too soon to know if the babies are cured, experts cautioned. But the experiment, reported in Friday's edition of the journal Science, finally provides evidence that gene therapy can succeed -- at a time when skeptics are harshly criticizing the field.

"The clinical benefits we observe had never been achieved before," Dr. Alain Fischer, the Paris physician who performed the gene therapy, said at a news conference Thursday, describing his sickly patients' rebound into healthy toddlers.

"It looks like this really worked," agreed Dr. Jennifer Puck, a geneticist at the U.S. National Institutes of Health who plans to start a similar gene therapy study this fall with doctors at North Carolina's Duke University. "This is a very important milestone."

The babies have SCID, or "severe combined immunodeficiency disease," a devastating, rare disease. Their bodies cannot make lymphocytes, the immune cells crucial for warding off infection -- meaning they can die from the most minor of germs.

The best-known victim of SCID was David, Houston's famous "bubble boy" who lived in a germ-proof plastic enclosure until his death at age 12.

Today, bone marrow transplants keep many SCID babies from having to live in sterile bubbles. Transplants provide them with healthy stem cells, special cells that reside in the bone marrow and produce lymphocytes. Transplants have cured some babies and extended the lives of others. But they're not always successful, so scientists hope gene therapy could offer an alternative.

The French babies never tried a transplant, and lived the first months of their lives inside sterile bubbles. They have the most common form of SCID, caused by a defective gene that blocks a cell receptor needed to trigger lymphocyte formation. Lift that roadblock, and the body should generate normal, working immune cells.

Fischer, of the Hopital Necker-Enfants Malades in Paris, took bone marrow from the babies when they were ages 8 months and 11 months, respectively. He culled some of their stem cells, and bathed them in fibronectin, a protein believed to make them more receptive to gene therapy.

Then he took a normal version of the immune system gene the babies were missing, and added it to a harmless virus. In a lab dish, he infected the babies' stem cells with the gene-carrying virus for three days. Then he transplanted the stem cells back into their bodies.

Soon, the babies started making germ-killing immune cells. Three months later, they went home from the hospital without antibiotics or any additional treatment -- and 11 months later, both have levels of immune system cells comparable to healthy children their age, Fischer said.

Neither suffered any side effects from the gene therapy. Their immune systems reacted properly when they were vaccinated against polio and other diseases. A third patient who had the treatment four months ago is also doing well, he said.

It is "the first significant success" in gene therapy in 10 years of experiments with over 4,000 people, said Dr. W. French Anderson of the University of Southern California, who performed the world's first gene therapy attempt.

What's especially important here: Scientists have long wanted to correct gene defects at the stem cell level because healthy stem cells should continue producing a working immune system for years. Plus, unlike the challenge with genetic diseases that affect other types of cells, every stem cell doesn't have to take up the new gene -- only a few healthy stem cells are required to work.

"You can't call it a cure" until the children are older and the disease doesn't return, Anderson cautioned, but it is a possibility. "It does look like gene therapy might finally be turning the corner."

If so, it comes at a crucial time. Gene therapy has come under harsh criticism since September, when a different gene therapy experiment killed an Arizona teen-ager. Skeptics questioned if the field was too risky and would ever cure anyone, and the public outcry slowed new experiments as regulators and doctors alike started double-checking safety procedures.

"I had my heart in my throat watching this trial go on," Puck said of the French study, worried that any side effects could threaten her own pending study. Instead, she said, "They did great."


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