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New therapeutic target identified in inherited brain tumor disorder

St. Louis, Nov. 1, 2005 -- Researchers studying a mouse model of neurofibromatosis 1 (NF1), a genetic condition that causes childhood brain tumors, have found their second new drug target in a year, a protein called methionine aminopeptidase-2 (MetAP2).

An established drug, fumagillin, is already known to suppress the activity of MetAP2. Researchers at Washington University School of Medicine in St. Louis showed that fumagillin significantly slowed the rapid proliferation of cultured mouse brain cells that resulted from the loss of Nf1, the gene that causes neurofibromatosis 1. Evaluation of the ability of this class of drugs to control brain tumor growth in small animal models is planned.

"This agent and others like it have already been in clinical trials as treatments for other tumors, so if we find that fumagillin inhibits brain tumor growth in preclinical studies, it will be a much smaller leap to using these compounds in patients with NF1," says senior investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology at Washington University School of Medicine in St. Louis and co-director of the neuro-oncology program at the Siteman Cancer Center.

Neurofibromatosis 1 affects more than 100,000 people in the United States and is one of the most common tumor predisposition syndromes. Gutmann and his colleagues discovered that abnormally high levels of MetAP2 may be a distinguishing characteristic of brain tumors in patients with NF1. Analyses of other similar brain tumors did not reveal the high MetAP2 levels characteristic of tumors caused by NF1.

To identify MetAP2, Gutmann collaborated with Jason D. Weber, Ph.D., assistant professor of medicine and of cellular biology and anatomy at the Washington University Neurofibromatosis Center. The center facilitates multidisciplinary neurofibromatosis research and is dedicated to developing better treatments to improve the lives of patients affected with neurofibromat
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
1-Nov-2005


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