"The positive effect of epothilone D on the function of axons and on cognition, without the onset of side-effects offers hope that this class of microtubule-stabilizing drugs could progress to testing in Alzheimer patients in the near future," says Lee.
"There are very few tau-focused drugs in clinical trials now for Alzheimer's disease," says Trojanowski. "While we and others have urged that pharmaceutical companies should not put all of their eggs in one drug basket to ensure the highest likelihood of finding disease-modifying therapies for Alzheimer's, we hope this successful mouse study of a tau drug will encourage more pharmaceutical companies to pursue programs on tau-focused drug discovery."
Help from Sponges
The epothilones are microtubule-binding drugs derived from marine sponges and have been used as anti-cancer drugs because they prevent cells from dividing. They do this by keeping microtubules overly stabilized, which blocks cell division and causes cell death in rapidly dividing cells such as cancer cells. However, since nerve cells do not replicate or divide, they are immune to the toxic effects of microtubule-binding drugs.
In Alzheimer's disease and other diseases with tau clumps in the brain, the hope is that a microtubule-stabilizing drug will restore the microtubule tracks to their original supportive structure. This led the researchers to give the tau mice epothilone D (epoD) to replace the now unavailable tau.
Indeed, epothilone D improved the brain function of tau mice, which have tau inclusions in their forebrain, degenerated axons, and broken microtubules. After treating three-month old male tau mice with a low dose of epoD once a week for three months, the mice showed increased numbers of microtubules and improved axon integrity, without notable side effects to organs and immune cells.
What's more, epothilone D reduced deficits in memory and learnin
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine