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Alzheimer's Disease Research
Current Award

Dr. David Harris

David Harris, M.D., Ph.D.

Boston University School of Medicine
Boston, MA

Title: Treating Alzheimer’s Disease with Prion Protein Ligands
Non-Technical Title: Treating Alzheimer’s Disease with Drugs Directed Against the Prion Protein

Duration: July 1, 2013 - June 30, 2016
Award Type: Standard
Award Amount: $250,000

Summary:

Alzheimer’s disease is a devastating disorder of memory that currently afflicts more than 5 million people in the U.S., and for which there is no effective cure. Dr. Harris’ team has identified a set of novel chemical compounds that bind to a key brain component called the prion protein, thereby possibly blocking its ability to produce toxic effects during Alzheimer’s disease. In this project, the team will pinpoint how these compounds interact with the prion protein, improve the chemical properties of these compounds, and test whether they can reverse nerve cell degeneration associated with Alzheimer’s disease. This work will help to establish whether these promising compounds will prove to be effective drugs for treatment of Alzheimer’s disease in human patients.

Details:

The goal of this project is to develop an entirely new class of therapeutic agents for Alzheimer’s disease, based on targeting a brain molecule called the prion protein (PrPC). PrPC was recently identified as an important component in the pathway by which beta-amyloid, a toxic protein, causes damage to nerve cells in Alzheimer’s disease. They have identified a set of chemical compounds that bind to PrPC, thereby potentially blocking the neurotoxic effects of the beta-amyloid peptide.

Dr. Harris’ team is now further characterizing how these compounds work, and studying their efficacy in biological test systems. The compounds they have identified are completely different from other therapeutic agents being used to treat Alzheimer’s disease, since they bind to a novel molecular target, PrPC, and they act by directly blocking pathways that lead to neurodegeneration. In contrast, most existing strategies rely upon inhibiting generation of beta-amyloid or enhancing its clearance from the brain. Once complete, these studies will establish the molecular mechanism by which PrPC-binding chemical compounds antagonize the effects of the beta-amyloid peptide, and will lay the groundwork for using these compounds to treat Alzheimer’s disease in humans.

Investigator Biography:

Dr. Harris is currently Professor and Chair of the Department of Biochemistry at Boston University School of Medicine. He earned his B.S. degree at Yale University, and his M.D. and Ph.D. degrees at Columbia University. He was a faculty member in the Department of Cell Biology and Physiology at Washington University in St. Louis for 19 years before moving to Boston University School of Medicine in 2009. Dr. Harris’ laboratory investigates the molecular and cellular mechanisms underlying two classes of human neurodegenerative disorders: Alzheimer’s disease and prion diseases. His group wishes to understand how Aβ, prions and other misfolded protein aggregates cause neuronal damage, and to use this knowledge to develop drug molecules and other therapeutic modalities for treatment of neurodegenerative disorders. Dr. Harris’ work is funded by grants from the National Institutes of Health and private foundations.