June 27, 2002
WASHINGTON (AP) - A single injection of genetically modified stem cells is all it took to cure two children of a complex form of an inherited immune system disorder often referred to as the "bubble boy disease,'' researchers report.

An experimental technique that altered genes in bone marrow stem cells restored the immune systems of the children, researchers from Italy and Israel said in a study appearing in the journal Science. The children were born with what experts said was the most complex form of severe combined immunodeficiency disorder, or SCID.

"Both children have been cured but ... both will be closely followed to see how it develops in the future," said Maria Grazia Roncarolo of the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

The children, who were seven months and 2 1/2 years old when the therapy began, were released with healthy, functioning immune systems between 15 months and 24 months ago, Roncarolo said in Milan.

Their form of SCID was caused by a gene flaw that blocks production of an enzyme called ADA, which is essential to make disease-fighting immune cells. The treatment consisted of injections of bone marrow stem cells that were altered to contain the missing enzyme gene.

French researchers announced in April that they had corrected genetic flaws in the immune systems of five boys who had X-linked SCID, the most common form of the immune system disorder.

Dr. W. French Anderson, a University of Southern California researcher and a pioneer in the field, said the new research is an important advance in gene therapy.

''It proves our basic premise that if you can get enough gene-engineered cells into the patient it will cure the disease,'' Anderson said in a telephone interview. Anderson was the first to try genetic engineering to cure ADA, or adenosine deaminase, form of SCID. His technique changed the gene in blood cells instead of the bone marrow. Two of Anderson's early patients have led normal lives since the 1990 procedure, but they require periodic shots of the ADA enzyme. He said the technique used by the Italian and Israeli researchers appears to be a cure that will require no more shots.

SCID strikes only about 50 children a year. In the past, the disorder was always fatal, with the children usually dying in infancy of uncontrollable infections. Starting in the 1960s, doctors treated SCID patients by isolating them in sterile environments. One of the most famous such patients was a Houston boy who spent all 12 years of his life in a plastic bubble filled with filtered air. Known as ''David the bubble boy,'' the youngster died in 1984 when, at his insistence, doctors tried a bone marrow transplant.

Since then, researchers have tried to cure some forms of SCID with gene therapy, but the new study is the first reported complete success for ADA-SCID, Anderson said.

Shimon Slavin of the Hadassah University Medical Center in Jerusalem and a co-author of the new study said one of the children - the fourth child born to an East Jerusalem Arab couple - had a quick recovery from the therapy. ''It was one small syringe of modified cells," Slavin said. ''No antibiotics, no blood transfusion, no fever.''

The second child in the study was the daughter of a Colombian family. She had been treated unsuccessfully in Miami and the family then sought gene therapy at San Raffaele.

''The girl can now have a normal life and has returned home," said Alessandro Aiuti of San Raffaele, first author of the study.

The researchers corrected the immune system disorder by changing the genes in the stem cells of the bone marrow that make blood cells.

To do this, the doctors removed stem cells from the bone marrow of each patient and then used a virus to insert into these cells the normal gene for ADA. The stem cells were then re-injected and naturally migrated to the bone marrow.

The children's bone marrow soon began producing normal disease-fighting blood cells. Within months, their immune systems were able to overcome some common childhood infections that previously had not responded to treatment.

The key to their success, said Anderson, may have been a novel use of a chemotherapy drug by the researchers. They injected both patients with the drug, which partially killed the youngsters' bone marrow. When the new stem cells were injected, the bone marrow was primed to use those cells to make new blood cells.

This allowed the injected stem cells to rapidly proliferate and become the dominant blood-making cells in the patients' body, Anderson said.

--- Associated Press writer Piero Valseechi in Milan, Italy, contributed to this report.

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