Gene therapy plus chemotherapy ups odds for success in treating 'bubble boy' disease

Beginning in 2001, researchers from the University of California Los Angeles and the National Human Genome Research Institute, a division of the National Institutes of Health, treated 10 patients with adenosine deaminase severe combined immunodeficiency (ADA-SCID), commonly referred to as bubble boy disease.

Four patients received ongoing enzyme replacement while six patients had their enzyme replacement therapy stopped and received low doses of chemotherapy, which reduces bone marrow density to create room for the transplanted cells to multiply. Fifty percent of the latter group demonstrated a restored immune response that parallels normal levels. The remaining patients show some independent production of the adenosine deaminase enzyme, but not enough to elicit independent immune responses.

"This trial extends prior findings and shows that ADA gene transfer can lead to restoration of a functionally protective immune system," said Donald Kohn, MD, the clinical trial sponsor and principal investigator at UCLA. "Because our trial was done in two phases, we can directly compare the effects of these approaches and show that withholding the enzyme and giving pre-transplant chemotherapy is markedly more effective."

Patients with ADA-SCID lack the enzyme adenosine deaminase and, as a result, have little or no immune system, leaving them vulnerable to infection and illness. ADA-SCID is one of the most promising conditions for treatment with gene therapy and has been the source of early successes in the field. Earlier trials in London and Milan have also showed restored immunity in patients treated with the gene therapy protocol.

A Phase II trial on the treatment is underway; three patients have been treated thus far. Research also continues into more efficient vectors for gene transfer, which scientists hope will result in a quicker, more robust immune response.