Collaborative MS Research Center Award
Thomas E. Lane, PhD
University of California, Irvine
George Chandy, MD, PhD
Michael Demetriou, MD, PhD
Steven S. Schreiber, MD
Michael Cahalan, PhD
Hans S. Keirstead, PhD
University of California, Irvine
A multifaceted effort to explore cell replacement strategies for repairing damage in MS.
Multiple sclerosis occurs when the immune system attacks and damages nerve fiber-ensheathing myelin and nerve fibers themselves. The promise of cell-replacement strategies to treat MS is significant: Imagine being able to infuse people with cells that could make new myelin, or transform into healthy nerve cells. But introducing new cells into humans also involves great risk. Developing safe and effective cellular therapies is a matter that demands tremendous focus.
This is the goal of the new Collaborative MS Research Center Award to Thomas E. Lane, PhD, at the University of California, Irvine. Dr. Lane’s team is investigating how to combine surgical implantation of immature cells with modulation of the immune attack – thus simultaneously promoting myelin repair while muting myelin damage.
Dr. Lane has extensive experience in animal models of both nerve cell loss/repair and T cell immunology, both areas that are extremely relevant to MS research. Recently he has also examined cell-replacement strategies for promoting myelin repair.
Dr. Lane is leading a project seeking to define key “chemokine receptors,” or messenger receivers that allow for migration of immature myelin-making cells (also known as oligodendrocyte progenitors, or OPCs) following transplantation into mice with established damage to myelin. Chemokines are immune chemicals that attract and assist the migration of the principle culprits of the immune attack in MS – T cells and macrophages – into the brain and spinal cord. Dr. Lane has previously been funded by the Society to study these chemicals and their receptors, or docking sites, for clues to stopping the influx of immune cells into the brain and spinal cord, but now is looking at them as possible vehicles for allowing the migration of therapeutic cells.
Dr. K. George Chandy is a professor in the department of physiology & biophysics, who pioneered the study of ion channels in the immune system. Ion channels are tiny pores on the surface of immune T cells that control the influx of charged particles and allow T cells to become activated. The project he is conducting in this collaboration focuses on mice with an MS-like disease called EAE. Dr. Chandy is evaluating the therapeutic potential of implanting OPCs while administering ion-channel blockers, which may turn down the immune attack while the cells go about the business of repair.
Dr. Michael Cahalan, professor and chair of the department of physiology & biophysics, is new to MS, but is also a pioneer in the study of ion channels and their function in the immune system. He is developing novel methods for tracking and visualizing the migration of stem and immune cells within the living nervous system.
Dr. Michael Demetriou is director of the Comprehensive MS Program, and has broad experience in T cell biology in MS and EAE. In this collaboration, Dr. Demetriou is investigating enzymes that exist on the surface of T cells and help to form carbohydrate molecules, and how such enzymes direct T cells. He is looking for clues to suppressing the damage that T cells incur in mice with EAE, and also is looking at a role these enzymes might play in directing transplanted OPCs.
Dr. Steven Schreiber is professor and chair of the department of neurology. His laboratory was the first to demonstrate activation of p53, a major regulator of cell death, in degenerating nerve cells. He brings this expertise to the field of MS research by examining how nicotinamide – which may inhibit p53 – may increase the repair capacity of nerve stem cells transplanted into mice with EAE.
These studies require major resources, in terms of cell populations for transplantation and imaging techniques. Collaborator Dr. Hans Keirstead, an associate professor of anatomy and neurobiology with extensive expertise in generating stem cell lines, is providing the cells that are proposed for these studies.
These projects cover the broad spectrum of efforts necessary to ensure the continued development of safe and effective cell-based strategies for treating people with MS.