(Philadelphia, PA) In a preclinical efficacy trial, the cancer drug paclitaxel (Paxceed)which exerts its effects by binding to and stabilizing microtubules inside cellsreduced the adverse effects of Alzheimer's disease (AD)-like pathology in a mouse model. Researchers from the University of Pennsylvania School of Medicine showed that the microtubule-stabilizing drug Paxceed helps correct the problems caused by clumped tau proteins in the nerve cells of mice. "Our hope is that microtubule-stabilizing drugs could be used to treat Alzheimer's and other related diseases," says John Q. Trojanowski, MD, PhD, Director of the Institute on Aging and Co-director of the Center for Neurodegenerative Disease Research and the Marian S. Ware Alzheimer Program at Penn. This research appears in the December 20 early online edition of the Proceedings of the National Academy of Sciences.

Tau amyloids are misshapened, insoluble proteins that clump in the brain and elsewhere and cause a host of debilitating diseases. Since many neurodegenerative diseases share or contribute to this pathology, the focus of therapy has been on drugs that break up these aggregates. Virginia M.-Y. Lee, PhD, Director of the Center for Neurodegenerative Disease Research, and Trojanowski introduced the concept of using microtubule-stabilizing drugs over a decade ago, and this is the first study to confirm their potential as a new class of drug for neurodegenerative disorders. "Now everyone is focused on drugs that disrupt the aggregated protein," says Trojanowski. "We're working on that too, but we also wanted to find a drug that replaces the clumped tau in sick neurons."

Microtubule-binding drugs derived from plants (taxol) and other biological organisms such as sponges (discodermolides) have been used as anti-cancer drugs because they prevent cells from dividing. They do this by keeping microtubules stabilized, which blocks cell division and causes cell death. Microtubules are protei
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
20-Dec-2004

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