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  Latest News  
  January 3, 2005
Volume 83, Number 01
p. 9


Cancer-fighting agent shows early promise as an Alzheimer's treatment

The widely used cancer drug paclitaxel (Taxol) has the potential to treat neurodegenerative disorders such as Alzheimer's disease, according to a preclinical proof-of-concept trial performed in mice [Proc. Natl. Acad. Sci. USA, published online Dec. 20, http://www.pnas.org/cgi/doi/10.1073/pnas.0406361102].

The research was spearheaded by John Q. Trojanowski, director of the Institute on Aging at the University of Pennsylvania School of Medicine, with support from Angiotech Pharmaceuticals, a manufacturer of paclitaxel. Trojanowski, who has been working with microtubule-stabilizing compounds for decades, says this is the first study to confirm the potential of microtubule-stabilizing compounds as a new class of drugs for treating neurodegenerative diseases.

Paclitaxel and other microtubule-binding drugs, such as the epothilones and the discodermolides, combat cancer by stabilizing a cancer cell's microtubules, thereby blocking cell division and causing the cells to die. Similarly, a protein called tau stabilizes the microtubule networks that act as a highway for axons in nerve cells. In neurodegenerative diseases like Alzheimer's, tau proteins become misfolded and form tangles in the brain's nerve cells. Without tau to stabilize the microtubules in the network, the transmission of nerve signals is lost.

"Think of tau as the cross-tie of the microtubule train track," Trojanowski explains. "The tracks will handle the traffic as long as they are parallel. If the cross-ties are missing, the tracks will wobble, and the train will run off the tracks."

The Penn research team demonstrated that in mice genetically engineered to have misfolded tau, paclitaxel can substitute for the microtubule-binding protein, thereby restoring the nerve signal network. This approach of trying to offset the loss of protein function is a novel way to tackle Alzheimer's, Trojanowski points out. Most other approaches aim to prevent or break up the aggregated proteins and plaques that characterize the disease, he explains.

The researchers say work needs to be done to create microtubule-binding compounds that cross the blood-brain barrier. But because paclitaxel is already approved to treat cancer, Trojanowski is hopeful that the drug and similarly approved microtubule-binding agents will move quickly into clinical trials for treating neurodegenerative disorders.

  Chemical & Engineering News
ISSN 0009-2347
Copyright © 2005

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