In Vivo Testing of Novel Tau Fibrillization Inhibitors
In the first 10 months of this program, Dr. Brunden’s team identified molecules that have desirable properties, including good brain levels in healthy mice, which suggested that these molecules were appropriate candidates for testing in mice with AD. However, additional research into these compounds and related analogues indicated that they act by an undesirable mechanism that would likely cause side-effects upon long-term administration. Therefore, the team has halted further optimization of these compounds, and will refocus their efforts on the identification of alternative compounds that prevent tau aggregate formation in a novel cell-based model. Use of this unique cell-based assay, in which NFT-like tau aggregates develop, will allow for the discovery of molecules that can reduce NFTs through multiple mechanisms. This approach could increase the likelihood of finding compounds that might ultimately lead to AD therapeutics.
About the Researcher
Dr. Kurt R. Brunden is Director of Drug Discovery and Research Associate Professor in the Center for Neurodegenerative Disease Research (CNDR) at the University of Pennsylvania. There he oversees drug discovery programs in the areas of Alzheimer's disease, Frontotemporal lobar degeneration, and Parkinson's disease. Brunden received his B.S. degree from Western Michigan University, with dual majors of biology and health chemistry. He obtained his Ph.D. in biochemistry from Purdue University and did a post-doctoral fellowship at the Mayo Clinic in Rochester, MN. Brunden joined the biochemistry faculty at the University of Mississippi Medical Center in 1988, with a research focus on the regulation of myelination.
He was recruited to the biotechnology sector in 1991, serving as vice president of Research at Gliatech, Inc. and later as senior vice president of Drug Discovery at Athersys, Inc. In these positions, he oversaw projects in Alzheimer's disease, cognition, schizophrenia, inflammation, and metabolic disease. Brunden was recruited to the University of Pennsylvania in 2007. He also serves as the chair of the NSD-C translational research study section for the National Institutes of Neurological Diseases and Stroke, is a reviewer and consultant for the Alzheimer's Drug Discovery Foundation, and is an ad hoc reviewer for several scientific journals. He has more than 65 publications, a number of issued U.S. patents, and several active patent applications.
First published on: July 6, 2011
Last modified on: June 2, 2011