Cancer Drug Effective in Mouse Model of Alzheimer's Disease

The experimental cancer drug epothilone D (EpoD), which acts by stabilizing microtubules, readily penetrates the blood brain barrier and blocks the formation of tau protein tangles, a characteristic of Alzheimer's disease.

The epothilones are a new class of cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials, epithilones have demonstrated better efficacy and milder adverse effects than taxanes. Another advantage of the epothiones is their ability to penetrate readily the blood brain barrier.

In the current study, investigators at the University of Pennsylvania (Philadelphia, USA) worked with the PS19 tau line of transgenic mice that develop forebrain tau inclusions, axonal degeneration, and microtubule defects. They treated three-month-old male PS19 mice with low doses of EpoD once weekly for a three-month period.

Results published in the October 13, 2010, issue of the Journal of Neuroscience revealed that this treatment improved central nervous system microtubule density and axonal integrity without inducing notable side effects. Moreover, EpoD treatment reduced cognitive deficits that were observed in the PS19 mice.

The authors concluded, "These results suggest that certain brain-penetrant microtubule-stabilizing agents might provide a viable therapeutic strategy for the treatment of Alzheimer's disease and frontotemporal dementias.”

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