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Important Notice: The Forum does not endorse any medical
product or therapy. ALL medications and supplements
should be taken ONLY under the supervision of a physician,
due to the possibility of side-effects, drug interactions,
etc.
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Name:
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epothilone D
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Other Names:
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BMS-241027, KOS-862
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Therapeutic Applications:
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Investigated for use in mild Alzheimer’s disease, potential application in other neurodegenerative tauopathies
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Therapy Types:
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small molecule
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Mechanisms:
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Epothilone D is a micotubule stabilizing agent
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Development Status:
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investigational in U.S.
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FDA Phase:
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Phase I
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Primary Medical Role:
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Investigated for use in colorectal cancer, lung cancer,
breast cancer, solid tumors, and prostate cancer.
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Role in Alzheimer's Disease:
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Alzheimer’s disease is characterized by insoluble deposits
of hyperphosphorylated tau protein within neurons.
Hyperphosphorylated tau is thought to contribute to disease
pathogenesis via both gain-of-function as well as
loss-of-function toxicities. Normal tau plays an important
role in stabilizing microtubules. When the function of
normal tau is compromised it leads to impaired axonal
transport and neuronal dysfunction. Epothilone is a
brain-penetrant microtubule-stabilizing agent which may
partially compensate for impaired tau function.
In studies in aged PS19 tauopathy mice, epothilone-treated
animals retained more healthy axons, lost fewer hippocampal
neurons, and performed better on memory tests compared to
vehicle-treated animals (Zhang et al., 2012).
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Companies:
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Bristol-Myers Squibb
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Notes:
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Bristol-Myers Squibb is currently enrolling for a Phase 1b
trial of epothilone D in mild AD patients. See
this
entry on Clinicaltrials.gov for more information.
For ARF coverage of this drug see ARF
conference news 2010 and ARF
conference news 2011
This entry was updated March 19, 2012.
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Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak
JS, Hogan AL, Xie SX, Ballatore C, Smith AB, Lee VM, Brunden
KR. The Microtubule-Stabilizing Agent, Epothilone D, Reduces
Axonal Dysfunction, Neurotoxicity, Cognitive Deficits, and
Alzheimer-Like Pathology in an Interventional Study with
Aged Tau Transgenic Mice. J Neurosci. 14 Mar
2012;32(11):3601-3611. Abstract
Brunden KR, Yao Y, Potuzak JS, Ferrer NI, Ballatore C, James
MJ, Hogan AM, Trojanowski JQ, Smith AB, Lee VM. The
characterization of microtubule-stabilizing drugs as
possible therapeutic agents for Alzheimer's disease and
related tauopathies. Pharmacol Res. 2011 Apr;63(4):341-51. Abstract
Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM,
Iba M, James MJ, Xie SX, Ballatore C, Smith AB, Lee VM,
Trojanowski JQ. Epothilone D improves microtubule density,
axonal integrity, and cognition in a transgenic mouse model
of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. Abstract
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