Collaborative MS Research Center Award
Funded in part through gifts from the Dan Family through the NMSS Greater Illinois Chapter
Bruce D. Trapp, PhD
Department of Neurosciences, Lerner Research Institute Cleveland Clinic Foundation
Wendy Macklin, PhD, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation
Andrei Gudkov, PhD, Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation
Robert Miller, PhD, Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio
To identify molecules that have the potential to therapeutically stimulate the repair of myelin damaged by MS.
Dr. Bruce Trapp and colleagues helped to change the course of MS research when, a few years ago, they reported finding that brain tissue from individuals with MS showed evidence of damage not only to the myelin that coats and insulates nerve fibers, but also to the wire-like nerve fibers themselves, which normally transmit nerve signals. This work has spurred investigations leading to the idea that nerve damage can occur frequently and early in MS, and that long-standing disability associated with MS might be the result of nerve, rather than myelin, damage. It has also underscored the need to protect myelin and to repair it when it is damaged, both to maintain proper nervous system function, and to help stave off nerve fiber damage that can lead to more permanent disability in MS.
The good news is that the body attempts to repair myelin damage and sometimes succeeds, especially early in the MS disease process. The aim of this new, five-year Collaborative MS Research Center award is to find ways to improve these natural repair processes so that they do a more complete job of restoring myelin and preserving neurological functions—findings that can ultimately be applied to people with MS.
Of primary focus in this quest are the immature myelin-producing cells resident in the brain which have the capacity to mature into replacement myelin-making cells called oligodendrocyte, and travel to sites of MS lesions where they are needed to promote tissue repair. The Center team is studying immature myelin "progenitor" cells in various stages of their development, in laboratory conditions and in animal models with MS-like disease. They have two central goals:
1) to understand genetic and other signals that, in normal development and in repair, direct progenitor cells to divide and multiply and differentiate into mature cells fully capable of making myelin; and
2) through a massive screening effort, to find specific molecules that can be used therapeutically to enhance and promote the formation of adult oligodendrocytes and myelin from these immature cells already resident in the brain.
This Center brings together four world-class scientists to bear on these important questions about preserving and protecting myelin: Drs. Trapp, Wendy Macklin, and Robert Miller are experts in MS-related central nervous system development and pathology, especially related to development and function of the oligodendrocytes that hold the key to central nervous system protection and repair. Dr. Andrei Gudkov is new to MS research, and brings expertise in identifying molecular targets for cancer treatment. His work in the Center focuses on searching for small molecules that influence the survival, growth and proliferation of progenitor cells that have the inherent capacity to become replacement cells that will form new myelin. Molecules that he discovers could become the basis for testing possible therapies for myelin protection and repair in MS.
Together, this Center's efforts will move the field of myelin protection and repair ahead by bringing into play the collective efforts and wisdom of established investigators on a crucial MS recovery problem.