Skip to main content
U.S. flag

An official website of the United States government

Epothilone D improves microtubule density, axonal integrity and cognition in a transgenic mouse model of tauopathy


Year of Publication:
Contact PI Name:
Kurt R. Brunden
Contact PI Affiliation:
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Bin Zhang, Jenna Carroll, Yuemang Yao, Justin S. Potuzak, Anne-Marie L. Hogan, Michiyo Iba, Michael J. James, Sharon X. Xiec, Carlo Ballatore, Amos B. Smith III, Virginia M-Y. Lee, John Q. Trojanowski
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

Neurons in the brains of those with Alzheimer’s disease (AD) and many frontotemporal dementias (FTDs) contain neurofibrillary tangles comprised of hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs), and tau misfolding could lead to a loss of this function with consequent MT destabilization, axonal integrity and neuronal dysfunction. One therapeutic hypothesis posits that MT-stabilizing drugs such as the anti-cancer drug epothilone D (EpoD). In this study the authors demonstrate that EpoD is brain-penetrant and that EpoD treatment of 3-month-old male PS19 mice, for a 3 month period, significantly improved CNS MT density and axonal integrity without inducing notable side-effects. Moreover, EpoD treatment reduced cognitive deficits that were observed in the PS19 mice. These results suggest that certain brain-penetrant MT-stabilizing agents might provide a viable therapeutic strategy for the treatment of AD and FTDs.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Epothilone D
Therapeutic Target:
Tubulin (Microtubules)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Barnes Maze
Motor Function
Rotarod Test
Electron Microscopy
Dystrophic Axons
Microtubule Density
Drug Concentration-Plasma
Drug Concentration-Brain
Body Weight
Organ Weight
Hematological Analysis/Blood Cell Count