Children with "bubble boy disease" believed to be cured by gene therapy.

Eight of 10 children who had the potentially fatal severe combined immunodeficiency (SCID), a form of the rare "bubble boy disease" appear to have been cured by gene therapy, according to a new study.

All 10 children who had SCID caused by a lack of adenosine deaminase were still alive a median of four years after the missing enzyme was replaced, Maria-Grazia-Roncarolo, MD, of the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, and colleagues reported in the January 29 issue of the New England Journal of Medicine (NEJM).

Bubble boy disease is a genetic disorder diagnosed in about 40 to 100 babies annually in the US. The nickname came from the experience of a Houston boy, David Vetter, who became famous for living behind plastic barriers to protect him from germs. He died in 1984 at age 12, according to the Associated Press.

None of the patients died developed leukemia, which has been a serious side effect in previous gene therapy studies in patients with X-linked SCID.

"Gene therapy restored normal function in five patients and resulted in significant improvement in lymphocyte counts and functions in the other five patients, leading to protection from infectious complications," the researchers said.

SCID due to a deficiency of adenosine deaminase is fatal if left untreated. It can be treated by a hematopoietic stem cell transplant from an HLA-identical sibling - the treatment of choice - or enzyme replacement therapy, although both treatments have limitations, according to the researchers. A transplant from a sibling is available for only a minority of the patients and enzyme-replacement therapy often does not sustain the correction of the immunodeficiency.

Four of the 10 patients had undergone a failed bone marrow transplant from a mismatched related donor and six had had an inadequate response to enzyme-replacement therapy.

Through the end of follow-up ranging from 1.8 to 8.0 years, eight of the patients no longer needed enzyme-replacement therapy and did not show signs of defective detoxification of purine metabolites, the researchers reported. The other two patients initiated replacement therapy after gene therapy, one at 4.8 months and one at 4.5 years.

Donald Kohn, MD, a SCID expert at Children's Hospital Los Angeles and the University of Southern California, said scientists are trying to understand why gene therapy produces a leukemia risk with the most common form of SCID but not the enzyme-related form. The new findings are good news for the idea of using gene therapy to treat some other blood disorders, including sickle cell disease, and studies should continue on gene therapy, Kohn said in an accompanying editorial in the NEJM.