Collaborative MS Research Center Award
$825,000; 4/1/08-3/31/13
Principal Investigator
Dennis Bourdette, MD
Co-Investigators
Gary Banker, PhD
Michael Forte, PhD
William Rooney, PhD
Lawrence Sherman, PhD
Purpose
Understanding MS damage that leads to progressive disability.
Summary
The theme of this five-year Collaborative MS Research Center is to investigate the role of dysfunction of mitochondria — tiny energy-producing batteries of cells — in the loss of nerve fibers (axons) in MS. Through interdisciplinary work of five strong investigators, this team is researching the interplay of calcium inside axons, mitochondrial dysfunction, deficits in production of ATP (an energy molecule) and abnormalities in axonal transport that are considered to be critical to the axonal degeneration responsible for long-term disability in MS.
The team is made up of experts in MS clinical disease and treatment, animal models, neuroscience and imaging techniques. The team’s goal is to establish an interactive set of complementary systems based in cultured brain cells, animal models and clinical studies involving MS subjects, in which to carefully assess mitochondrial function during MS disease processes and the consequences of mitochondrial dysfunction as it relates to axonal degeneration in MS.
Center leader Dennis Bourdette, MD, is Chairman and the Roy and Eulalia Swank Family Research Professor in the OHSU Department of Neurology, Co-Director of the VA MS Center Excellence-West and a faculty member of the Neurosciences Graduate Program. He has extensive experience in conducting clinical research in MS and using EAE models to develop new therapeutic approaches for MS.
Dr. Bourdette is collaborating with Michael Forte, PhD, a neuroscientist and geneticist who is engaged in research studying mitochondria and experienced in the design of breeding strategies for the creation of genetically-modified mice to address specific research questions. Together they are studying axonal injury in EAE. Another collaborator is Lawrence Sherman, PhD, a molecular neuroscientist who has extensive experience developing mouse models of MS and studying the mechanisms of development of myelin-making cells (oligodendrocytes) and failure of myelin repair.
William Rooney, PhD, is a magnetic resonance imaging scientist who has extensive experience in using novel MRI/MRS techniques in human and animal studies. With his help, the team will be using the very strong 7 Tesla MRI device to assess regional ATP changes in the brains of people with MS.
Dr. Rooney is also teaming up with Drs. Sherman, Forte and Bourdette in using the even stronger, 12 Tesla MRI instrument to measure axonal changes, ATP and other chemicals in genetically altered mice. Gary Banker, PhD, is a pre-eminent neuroscientist who is new to the MS field. He has developed novel imaging techniques to assess transport of cell components along axons. Dr. Banker is providing dual expertise in conducting research on axons and the use and development of novel imaging approaches to studying neuronal function. Dr. Banker is collaborating with Drs. Forte and Sherman in assessing how mitochondrial dysfunction and aspects of the immune attack in MS alter axonal transport.
The long-term goal is to use this interactive experimental strategy to develop and test therapies that reverse mitochondrial dysfunction, in hopes of protecting axons from degeneration and thereby preventing disease progression.