WASHINGTON — Using an experimental technique that altered genes in bone-marrow stem cells, doctors cured two children who were born with the "bubble boy" disease that leaves patients defenseless against infection.
The children were born with a form of severe combined immunodeficiency disorder caused by a gene flaw that blocks production of an enzyme called ADA, which is essential to make disease-fighting immune cells.
Doctors in Italy and Israel cured the children with injections of bone-marrow stem cells that had been altered to contain the missing enzyme gene. In a matter of months, the researchers report in this week's edition of the journal Science, both children had healthy immune systems.
Dr. W. French Anderson, a University of Southern California researcher and a pioneer in the field, said the research is an important advance for the entire concept of gene therapy.
"This gives a boost to the whole field because 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 Wednesday. "That is very important, and therefore this is a very exciting paper."
Anderson was the first to try genetic engineering to cure the ADA, or adenosine deaminase, form of severe combined immunodeficiency disorder, or 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 ADA enzyme to assure healthy immune systems.
The technique used by the Italian and Israeli researchers, Anderson said, appears to be a cure that will require no further shots.
"That means that these patients have normal functioning immune system," he said. Technically, Anderson added, the cure cannot be considered complete for many decades while doctors monitor the patients, but for all intents and purposes it is a cure.
SCID is rare, striking 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. He became known as "David the bubble boy." He died in 1984 when, at his insistence, doctors tried a bone marrow transplant.
Since then, a number of researchers have tried to cure some forms of SCID with gene therapy. At least a handful of patients appear to have developed healthy immune systems after gene therapy for one type of SCID, called gamma C.
But the new study is the first to report a cure for ADA-SCIDS, the most complex form of the immune system disorder, Anderson said.
In the new study, the Italian and Israeli researchers treated two children, a seven-month-old and 2 1/2-year-old, who were born without functioning normal ADA enzyme genes.
The researchers corrected the inherited flaw 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 where then re-injected and naturally migrated to the bone marrow.
The researchers report in the journal Science that shortly after the procedure, the bone marrow in both children 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. They were even able to be successfully immunized against tetanus.
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.
Claudio Bordignon of the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, was the senior author of the study. The senior Israeli researcher was Prof. Shimon Slavin of the Hadassah University Medical Center in Jerusalem.
On the Net: Science: www.sciencemag.org