Jewish World Review June 28, 2002 / 18 Tamuz, 5762

Gene therapy cures immune disease in kids

By Charles Choi | (UPI) A new gene therapy technique has rewritten the DNA of bone marrow cells in two young children suffering from a rare and debilitating disease, boosting their severely weakened immune systems and offering them the promise of a more normal life, Italian researchers report.

Not only does this technique offer immune-system-dysfunctional children a life outside the confines of their sterile "bubbles," the team that performed the procedure said, but it also could help combat a host of other blood system and immunodeficiency disorders.

"The most immediate extension is going to be AIDS gene therapy," Claudio Bordignon, a gene therapist at the San Raffaele-Telethon Institute for Gene Therapy, told United Press International. "The trial is already approved by the Italian authorities and is expected to start in mid July."

The two children -- one 7 months old, the other 2 years old -- suffer from a rare severe immunodeficiency disorder known as ADA-SCID. It usually confines its patients within sterile environments to protect them from infections. The disease prevents its victims from producing an enzyme known as ADA, which is critical for manufacturing infection-fighting agents. About 30 to 50 babies are born with ADA-SCID worldwide each year.

Regular injections of bovine ADA can control the disease to a certain degree, as can bone marrow transplants. However, bovine ADA injections are expensive, and bone marrow donors are not always available. Also, bone marrow transplants can prove toxic, sometimes triggering a dangerous disease called graft versus host, or GVH, in which the body becomes a battleground as donor cells fight host tissues for domination.

"With gene therapy you can treat every patient, and the toxicity is enormously lower than for bone marrow transplants," Bordignon said.

Gene therapy uses modified viruses to rewrite the DNA of cells to replace defective genes with healthy ones. The researchers removed some bone marrow from the two children and isolated the blood stem cells inside. Blood stem cells are the primordial tissue from which the body's red and white blood cells originate.

The team used a virus to infect the blood stem cells with a healthy version of the ADA gene. Before they injected the stem cells back into the patients, the scientists gave the children a small dose of a transplant drug "to make space for engineered marrow to seize, expand and grow better," Bordignon explained.

Bordignon said this additional step made his team's work succeed where previous gene therapy efforts to treat immune diseases fell short. Within weeks after injection, the engineered stem cells migrated into the bone marrow and began generating key types of immune cells. Within months, antibodies appeared and the patients responded normally to tetanus vaccination. After a year, the older child no longer had the respiratory ailments, chronic diarrhea or scabies that were common before the treatment began.

"It's a very exciting achievement that's certainly unprecedented in this disease, a clear advance over previous attempts," immunologist Fabio Candotti of the National Human Genome Research Institute in Bethesda, Md., told UPI.

The children are now living and developing normally thanks to their gene therapy. Before this therapy can find widespread use, however, Bordignon stressed clinical studies on more volunteers are needed to test for safety and effectiveness. For instance, he said, the transplant drug given to the children might have long-term toxic effects.

"However, the low dose utilized in the study should significantly reduce the risk, that is in my opinion fully justified in the treatment of severe life-threatening disorders," he noted. In addition to the AIDS gene therapy tests that are beginning in July, Bordignon said his team plans to use the technique to treat other severe immunodeficiency diseases and will work on blood system disorders as well.

Candotti cautioned, however, that biological differences in diseases might require significant changes in the treatment.

The researchers describe their findings in the June 28 issue of the journal Science.

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© 2002, United Press International