Modified stem cells protect healthy tissue from brain cancer treatment

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Drug treatment for glioblastoma may be made more effective by introducing a chemotherapy-resistant gene into normal bone marrow stem cells to protect them from the toxic effects of chemotherapy.

Median survival for persons with glioblastoma is just 12 to 15 months, in part because there is no cure for the disease but also because the treatment that does exist cannot be used effectively: The temozolomide chemotherapy regimen has to be accompanied by benzylguanine, because the second drug counteracts the chemotherapy-resistant gene MGMT. Glioblastoma cells produce a large amount of MGMT, but the protein is also present in normal blood and bone marrow cells. Benzylguanine disables MGMT in both diseased and healthy cells, making both susceptible to the harmful effects of treatment. This means chemotherapy cannot be administered to the desired extent.

However, researchers at the Fred Hutchinson Cancer Research Center in Seattle, Washington, recently reported encouraging results from a clinical trial involving four persons with glioblastoma. In the trial, patients' bone marrow stem cells were removed and modified with a retrovirus vector to keep them chemotherapy-resistant in the face of benzylguanine administration. The cells were then reinfused into the patients.

The gene-modified stem cells persisted for more than a year, with patients suffering no apparent harmful effects.

“Our initial results are encouraging because our first patient is still alive and without evidence of disease progression almost 2 years after diagnosis,” noted investigator Hans-Peter Kiem, MD, in a statement describing his team's findings, which were presented at the annual meeting of the American Society of Gene and Cell Therapy, held May 18-21, 2011, in Seattle.

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