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Alzheimer's Disease Research - Current Award

Dr. Kiran Bhaskar

Kiran Bhaskar, Ph.D.

Lerner Research Institute at Cleveland Clinic
Cleveland, OH, United States

Title: Role of p38 MAPK in the Microglial-Mediated Alzheimer's Disease Tau Pathology
Non-Technical Title: The Role of p38 MAPK as a Putative Drug Target Against Alzheimer's Disease Tangle Pathology

Duration: July 1, 2011 - June 30, 2013
Award Type: Pilot
Award Amount: 150,000


Summary:

In a recent study (published in October 7th, 2010 issue of the journal NEURON), we have identified p38 MAPK as a link between neuroinflammation, cell-autonomous to microglia, and Alzheimer's disease tau pathology. In the current study, the role of a safe, orally bioavailable and brain permeable p38 MAPK inhibitor (MW01-2-069A-SRM) in preventing tau pathology will be examined both in vitro utilizing primary neurons and in vivo utilizing a unique transgenic mouse model of tauopathy (hTau mice).

Details:

Dr. Kiran Bhaskar’s laboratory has already shown that inflammation by a particular immune cell, called microglia, can start and accelerate tangles in cell cultures and in a transgenic mouse model of Alzheimer’s disease. A protein, called p38 MAPK, is involved with this inflammation and subsequent creation of tangles. Dr. Bhaskar and collaborators will determine whether a drug, called 069A, will target the p38 MAPK protein and prevent tangles from forming in the brains of mice with a human form of Alzheimer’s disease. Collaborators have adapted the 069A drug to enable it to be taken by mouth and get into the brain. If an experimental increase in p38 MAPK causes an increase in tangles and intervention with 069A prevents it, then a future goal would be to test this drug in a human clinical trial for treatment of Alzheimer’s disease.

Investigator Biography:

Dr. Kiran Bhaskar is a Project Staff Scientist in the Department of Neurosciences at the Lerner Research Institute, Cleveland Clinic Foundation. Prior to this, Bhaskar was a Research Associate at the Cleveland Clinic and postdoctoral fellow at the University of Iowa, Carver College of Medicine. Bhaskar’s laboratory focuses on understanding the role of neuroinflammation in Alzheimer’s Disease (AD) tangle pathology utilizing various cell culture and transgenic animal models of AD. Following the recent discovery that brain inflammation plays a causal role in AD-related tangle pathology, Bhaskar and his group are currently testing several drug candidates as potential therapies against inflammation-induced tangle pathology.