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Screen finds an antidepressant and other drugs
Date:9/14/2011

NEW YORK, September 14, 2011In a new study NYU School of Medicine researchers report that they have found several chemical compounds, including an antidepressant, that have powerful effects against brain-destroying prion infections in mice, opening the door to potential treatments for human prion diseases.

The researchers, led by Thomas Wisniewski, MD, professor of neurology, pathology and psychiatry, report their findings in today's online edition of PLoS One. Prion diseases are a family of rare progressive neurodegenerative disorders that affect both humans and animals. An unusual infectious agent, a priona misshapen version of a normal cellular proteincauses the fatal disorders. There are no treatments.

The researchers found that trimipramine, an antidepressant, and fluphenazine, an antipsychotic, have activity against prions. Since the drugs are already in clinical use, Dr. Wisniewski believes that doctors can test them in human patients with Creutzfeldt-Jakob disease, the most common human prion disease.

Dr. Wisniewski and his colleagues previously found 68 chemical compounds, known as styryl-based compounds, bound tightly to amyloid-beta protein deposits in the brains of people who died of Alzheimer's disease. Since the disease-causing aggregates of amyloid-beta and prion proteins are widely believed to have similar structures, his team screened these 68 styryl-based compounds for their ability to inhibit prion infection in a standard cell culture. They found two that seemed both effective and non-toxic, and confirmed their effectiveness by showing that on average they markedly delayed the onset of symptoms in prion-injected lab mice. The styryl-based compounds also reduced the signs of disease in the mouse brains.

Dr. Wisniewski's team found similar results the antidepressant trimipramine and the anti-schizophrenia drug fluphenazine. Both are chemically related to the anti-protozoal drug quinacrine, which is
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Contact: Christopher Rucas
Christopher.Rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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