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Research Grants - 2013


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Research Grants 2013


To view an abstract, select an author from the vertical list on the left.

2013 Grants - Boxer

Phase I Multiple Ascending Dose Trial of the MT Stabilizer TPI-287 for AD

Adam L. Boxer, M.D, Ph.D.
University of California, San Francisco
San Francisco, California

2013 Part the Cloud Translational Research for Alzheimer's Disease

Microtubules (MT) are small, tube-like structures that act like a skeleton inside cells, maintaining cell structure and helping to transport nutrients throughout the cell. The protein tau attaches to microtubules where it also helps in maintaining cell structure and transporting nutrients.

Microtubules are dynamic structures, being broken down and rebuilt continually. There is some evidence that microtubules are unstable in Alzheimer's disease, being broken down at a faster rate than they are rebuilt, or being rebuilt incorrectly. When such instability occurs, it may lead to abnormal clumping of tau, which can then form neurofibrillary tangles, one of the characteristic features of Alzheimer's disease.

Adam L. Boxer, M.D., Ph.D., and colleagues have been studying drugs that stabilize microtubules. Studies in animal models of Alzheimer's disease suggest that such drugs may inhibit the development of neurofibrillary tangles and preserve the function of nerve cells. One of the most promising drugs of this type is known as TPI-287. TPI-287 is a new drug that was originally developed to treat brain cancer, but may also stabilize and restore the function of microtubules at much lower doses than used for cancer chemotherapy. TPI-287 is still being tested for use in cancer, but so far seems to be well tolerated and easily gets into the brain.

Dr. Boxer and colleagues have proposed a phase I clinical trial of TPI-287 in people with mild to moderate Alzheimer's disease. Phase I trials represent the first tests of a drug in humans. Their purpose is to determine safe doses and side effects from the drug. Dr. Boxer's team plans to study several doses of TPI-287 to determine which doses are safe to use, how the drug is processed by the body, and to begin examining whether safe doses have beneficial effects. These studies may lead to more extensive phase II and phase III trials, in which the drug's effectiveness will be tested more rigorously.