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Targeted Research Promise 2010

The National MS Society's bold new initiative for nervous system repair and protection in MS involves the largest grants ever offered by the Society and sets the stage for translating basic lab discoveries into clinical efforts to restore nerve function in people with MS. Four multinational, interdisciplinary teams are developing non-invasive tools and models, and designing clinical trials to pave the way for clinical testing to restore function in people with MS.

Principal Investigator
Dr. Peter A. Calabresi Peter A. Calabresi, MD
Johns Hopkins University School of Medicine
Baltimore, MD

$4.8 million (out of a total of $15.6 million for the Repair and Protection initiative)

Research Team  
Katherine Conant, MD
John W. Griffin, MD
Norman Haughey, PhD
Paul Hoffman, MD, PhD
Craig Jones, PhD
Douglas A. Kerr, MD, PhD
Sanjay Keswani, MBBS, MRCP
Justin C. McArthur, MBBS, MPH
Susumu Mori, PhD
Avindra Nath, MD
Thien Nguyen, MD, PhD
Peter Van Zijl, PhD
Johns Hopkins University School of Medicine, Baltimore, MD
Laura Balcer, MD, MSCE
University of Pennsylvania School of Medicine
Philadelphia, PA

Kathy Zackowski, PhD
Kennedy Krieger Institute
Baltimore, MD

Gary R. Cutter, PhD
The University of Alabama at Birmingham
Birmingham, AL

Searching for better ways to detect and quantify nerve fiber injury in MS and testing agents that may protect the nervous system from further damage.

Multiple sclerosis occurs when the immune system attacks the myelin coating that insulates nerve fibers in the brain and spinal cord, and can also damage the nerve fibers themselves. Recent reports indicate that it is the damage to nerve fibers—axons—that underlies the progressive disability experienced by people with MS. However, the mechanisms that lead to axonal injury in MS remain largely unknown.

Peter A. Calabresi, MD, has assembled a team to investigate the pathways of axonal injury, with funding from the National MS Society's "Promise 2010" Campaign. Dr. Calabresi has strong ties to the National MS Society, as both a chapter volunteer advisor and for the Society's headquarters as a peer reviewer. In 2004 Dr. Calabresi received a Collaborative MS Research Center Award from the National MS Society, bringing together both established and developing scientists—with expertise in MS and other diseases - to focus on mechanisms that underlie nerve fiber injury in MS and to use this knowledge to develop therapies that diminish disease progression. Now some of those same team experts are participating in the repair initiative.

The team is investigating two possibilities: that axons degenerate in MS because of the loss of structural support offered by myelin, or that the loss of myelin exposes the axon to injury from the immune attack.

Dr. Calabresi and colleagues are examining these possibilities in rodent models in which myelin formation is disrupted. They have preliminary evidence that axons are affected in these models, and are investigating the mechanisms by which this may occur. They also are testing the effects of the immune attack on axons in rodent models of nervous system inflammation, and in a novel "co-culture" of nerve cells and immune cells in lab dishes which they have created to determine how immune cells may damage nerve cells.

Dr. Calabresi's team also is developing new methods of assessing the damage that occurs to axons in people with MS, including high-resolution imaging techniques, and a method of specifically quantifying axonal damage in the optic nerve. The ultimate goal is to carry out pilot clinical trials of agents that may protect nerve fibers from damage. They are using information gained from the preclinical and imaging studies to guide the design of these future clinical trials.

"We are carrying out a series of experiments to define the cellular and molecular pathways of nerve fiber injury in MS," Dr. Calabresis says. "We also are developing new imaging methods to detect and quantify nerve fiber injury, and using these measures, we will perform pilot studies of promising agents in people with MS."

Dr. Calabresi is an MS neurologist who has assembled a team of highly experienced basic scientists and clinicians whose research expertise ranges from cellular biology to advanced imaging techniques. Many are new to the field of MS, although well-funded and well-recognized in their respective fields.

These researchers are sure to glean information that will expedite the development of neuroprotective agents, and advance them to clinical trials in people with MS. This effort complements those of the three other repair teams. All four teams will come together on a regular basis to enhance collaboration and sharing of ideas and progress.

  Last updated August 3, 2005