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Collaborative MS Research Center Awards > Segal Team

Collaborative MS Research Center Award
$825,000; 4/1/06-3/31/11

Principal Investigator
Benjamin M. Segal, MD

Benjamin M. Segal, MD
University of Rochester Medical Center, Rochester, NY



Steven Schwid, MD
Andrew Goodman, MD
Michael K. O'Banion, MD, PhD
Steven Dewhurst, PhD
Roman Giger, PhD
William Bowers, PhD
University of Rochester Medical Center, Rochester, NY

Howard Federoff, MD, PhD
Tim Mosmann, PhD
University of Rochester Medical Center, Rochester, NY

Developing therapeutic vaccines and novel immune-modulating agents to improve the treatment of MS and advance nervous tissue repair.

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, with funding from a Collaborative MS Research Center Award. His team brings together senior and developing investigators at the University of Rochester Medical Center, some of whom have extensive experience in MS research and others who are new to the field.

In one project, Dr. Segal is investigating the role of two immune messenger proteins in MS. One, called IL-23, is critical to the development of EAE, an MS-like disease, in mice. Recent evidence suggests that another messenger protein, called IL-1 beta, causes nerve tissue damage, and might be released as a result of IL-23 activity. Dr. Segal is joining with Michael K. O'Banion, MD, PhD, whose groundbreaking work in neurobiology identified the molecule COX -2 as a target for anti-inflammatory therapies. Drs. Segal and O'Banion are examining the activity of IL-23 and IL-1 beta closely in mouse models developed by Dr. O'Banion, and in cells taken from people with MS. The results may present a more specific target for MS immunotherapy.

A second project focuses on altered peptide ligands (APLs, modified portions of a protein. In MS, APLs of myelin proteins have been used therapeutically to alter immune responses). Dr. Segal and Steven Dewhurst, PhD, are combining efforts to explore a novel strategy in which APLs are administered in small quantities using a protein that efficiently targets their delivery. Dr. Dewhurst is a highly experienced virologist whose research has focused on vaccine delivery. The team is evaluating this strategy in EAE.

A third project focuses on growing evidence supporting the use of vaccines against "Nogo," a protein found in myelin that actually 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, and William Bowers, PhD, are collaborating to develop vaccines that target and block specific Nogo molecules. Dr. Giger is a pioneer in Nogo research, and Dr. Bowers' research focuses on gene transfer technologies. Nogo vaccines will be assessed for their ability to limit nerve fiber damage when administered during different stages of EAE.

Also joining the team is Steven Schwid, MD, the Chair of the MS Cooperative Research group (MS- CORE ), a consortium that fosters investigator-led multicenter research in MS. Dr. Schwid's role on this team is to provide guidance on the clinical relevance of research supported by the Center, and he will help the team to develop and conduct clinical trials of promising therapies through MS- CORE. Andrew Goodman, MD, Director of the MS Clinic at Rochester, has extensive experience in the design and implementation of clinical trials in MS, and will act in concert with Dr. Schwid to assess the clinical implications of research projects and to help move preclinical discoveries towards clinical trials.

Each of these projects builds upon existing strengths at the University of Rochester Medical Center in vaccine biology, cellular and molecular immunology, virology, and clinical MS research, to develop novel, cutting-edge therapies that are tailored for people with MS.

  Last updated March 27, 2006