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Discovery In "Bubble Boy" Disease Gene Therapy

Researchers at St. Jude Children's Research Hospital have created a mouse model of a debilitating disease of the immune system that could offer clues about //the gene therapy used to treat children that caused leukemia in some cases. The disease, named as X-linked severe combined immunodeficiency (XSCID), is set into action by a mutation in a gene called gamma C that obstructs the immune system from forming B and T lymphocytes.

B-lymphocytes produce antibodies, and T lymphocytes perform a variety of tasks such as helping B cells and killing cells that are infected with viruses. XSCID was made famous by the story of the so-called "Bubble Boy" who lived inside a plastic "bubble" to shield him from infections.

Based on these recent studies, the St. Jude researchers concluded that XSCID itself makes mice--and by extension, children with this disease--particularly susceptible to cancer caused by gene therapy.

One important implication of this finding is that gene therapy for other forms of genetic blood diseases will pose significantly less risk for causing cancer than was previously thought, according to Brian Sorrentino, M.D., director of St. Jude Experimental Hematology Division and co-director of Transplantation and Gene Therapy. Sorrentino is senior author of a report on these findings that appears in the August issue of Proceedings of the National Academy of Sciences.

"Our current findings with this new mouse model offer real hope that we can make gene therapy for X-linked SCID safe as well as effective," said Yan Shou, Ph.D., the paper's first author and the major contributor to this work. XSCID was the first disease ever successfully treated with gene therapy. In 2002, French researchers inserted normal gamma C genes into bone marrow stem cells removed from young children with the disease. The clinicians then infused the genetically modified stem cells back into the patients, restoring the ability of nine child
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