Collaborative MS Research Center Award
$713,330; 4/1/06-3/31/11
Principal Investigator
Benjamin M. Segal, MD
University of Michigan, Ann Arbor, MI
Co-investigators
David Irani, MD, PhD
Yasmina Laouar, PhD
Anushka Andjelkovic, PhD
Roman Giger, PhD
Lori Isom, PhD
Marina Mata, MD
Ronald Bucanovich, MD, PhD
Robert Zand, PhD
David Fink, MD
University of Michigan, Ann Arbor, MI
Purpose
Developing therapeutic vaccines and novel immune-modulating agents to improve the treatment of MS and advance nervous tissue repair.
Summary
Multiple sclerosis occurs when an immune attack is launched on nerve fibers and their myelin insulation in the brain and spinal cord. Long-term disability occurs when myelin and nerve fibers fail to repair and regenerate. Because the disease-modifying agents that are currently FDA-approved for the treatment of MS are only partially effective, there is a clear need for new therapies that target the specific immune system components that sustain inflammation, on the one hand, and promote the protection and regeneration of myelin and nerve fibers, on the other.
In response to this challenge, Benjamin M. Segal, MD, a former Harry Weaver Neuroscience Scholar of the National MS Society, is seeking to develop therapeutic vaccines and novel immune-modulating agents for MS. His team brings together senior and developing investigators at the University of Michigan.
Dr. Segal is joining with Yasmina Laouar, PhD, to investigate the role of the immune messenger protein TGF-beta in modulating immune cells during the autoimmune attack in MS. She is an immunologist new to MS, who has engineered mouse models designed to study TGF-beta. TGF-beta may be a critical factor in inhibiting the activity of Th17 cells, which are strongly implicated in the development of MS. The results of this study can inform the development of novel immunomodulatory agents and therapeutic vaccines that might exploit TGF-beta signals.
Dr. Segal and Anushka Andjelkovic, PhD, are combining efforts to investigate trafficking to the brain and spinal cord during EAE, an MS-like disease. Dr. Andjelkovic, also new to MS, is an expert on the blood-brain barrier (BBB, the lining of cells that should protect the brain from intruders) and factors that control its permeability. Specifically, these colleagues are looking at immune proteins known as chemokines that may modulate immune cell traffic into the brain. These studies can instruct the design of immunomodulatory agents that prevent BBB breakdown. Drs. Segal and Andjelkovic are being joined in their efforts by Ronald Bucanovich, MD, PhD, and Robert Zand, PhD, experts in tumor immunity and biochemistry, respectively, who have interests in the factors that control permeability, such as vascular endothelial growth factor (VEGF).
A third project focuses on growing evidence supporting the use of vaccines against "Nogo," a protein found in myelin that inhibits regrowth of nerve fibers. But this has proven to be a complicated effort, as some molecules associated with Nogo may be protective. Roman Giger, PhD, is developing vaccines that target and block specific Nogo molecules. Dr. Giger is a pioneer in Nogo research. Nogo vaccines are being assessed for their ability to limit nerve fiber damage when administered during different stages of EAE. He is collaborating with Marina Mata, MD, and David Fink, MD, neurologists and scientists who have extensive expertise in the construction and therapeutic employment of similar vaccines.
David Irani, MD, PhD, a clinician with expertise in MS, is facilitating translational research and early clinical trials that arise from this center's studies.
Lori Isom, PhD, an expert MS researcher who is studying how to regulate ion channels to protect nerve fibers from injury, is participating in research forums and is sitting on a committee that judges pilot projects for the Collaborative Research Center.
Each of these projects builds upon existing strengths at the University of Michigan in cellular and molecular immunology, virology, and basic and clinical MS research, to develop novel, cutting-edge therapies that are tailored for people with MS.