Collaborative MS Research Center Award
$742,500;11/1/09-10/31/14
Principal Investigator
Moses Rodriguez, MD
Mayo Clinic and Foundation
Rochester, MN
Purpose
Explore the molecular signals that might stimulate or inhibit repair processes in MS, for clues to developing therapeutic strategies to promote repair.
Co-investigators
Allan J. Bieber, PhD
Dan Billadeau, PhD
Karen Hedin, PhD
Charles L. Howe, PhD
Claudia Lucchinetti, MD
Slobodan Macura, PhD
James Maher III, PhD
Richard Pagano, PhD
Isobel Scarisbrick, PhD
Art Warrington, PhD
Mayo Clinic and Foundation
Rochester, MN
Summary
Multiple sclerosis occurs when the immune system attacks and damages the brain and spinal cord, specifically nerve fiber-insulating myelin, also damaging nerve fibers themselves. Numerous molecules from the immune and nervous system participate in this attack, and research on some of these pathways already has yielded approved MS treatments. Moses Rodriguez, MD, is building upon a team he created with previous Collaborative MS Research Center Award, and is now expanding and strengthening that team to explore these signals in MS models and in human MS tissue.
The first project brings in a new face to MS research as a collaborator – Karen Hedin, PhD, an expert in the signaling pathways of immune molecules known as chemokines. Research indicates that signals from these molecules may improve the function of nerve cells and protect them from death. Dr. Hedin will used advanced biochemical and molecular techniques to investigate this possibility in nerve cells isolated in the laboratory.
Another project has attracted another new face to MS research. Daniel Billadeau, PhD, is an expert in signals sent by the molecule glycogen synthase kinase 3 (GSK3). This molecule has been shown to be important in increasing the proliferation of cancer cells. Dr. Billadeau is examining whether inhibiting GSK3 will prove to be an effective strategy in models of MS-like disease and tissue from areas of disease activity in people with MS.
Isobel Scarisbrick, PhD, an experienced MS researcher, joins the team as well. Dr. Scarisbrick is investigating a newly identified enzyme family, the kallikreins, to clarify their role in the development of MS. Preliminary evidence indicates that kallikreins were more active in people with progressive courses of MS. This project aims to further define how kallikreins may promote damage in MS models and human tissue and whether this can be prevented with inhibitors.
The remaining members of the team are providing crucial support for these projects: Dr. Rodriguez and Allan Bieber, PhD, as experts in animal models of MS, and Claudia Lucchinetti, MD – lead investigator of the MS Lesion Project funded through the Society’s Promise: 2010 campaign – as an authority on MS development and a source of tissue samples from people with MS. Charles Howe, PhD, is lending his experience in characterizing and quantifying damage to nerve fibers. Art Warrington, PhD, is a source of expertise in preparing cultures of nerve and myelin-making cells in the laboratory.
With his previous Center Award funding, Dr. Rodriguez identified an antibody that promotes myelin repair. The tight-knit Mayo group already houses the MS Lesion Project and the Mayo Center for Pediatric MS – also funded through Promise: 2010. Dr. Rodriguez’s Collaborative MS Research Center Award promises to join these initiatives in moving us closer to a world free of MS.