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.
$4.8 million (out of a total of $15.6 million for the Repair and Protection
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
Balcer, MD, MSCE
University of Pennsylvania School of Medicine
Kennedy Krieger Institute
Gary R. Cutter,
The University of Alabama at Birmingham
Searching for better ways to detect and quantify nerve fiber injury in
MS and testing agents that may protect the nervous system from further
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 fibersaxonsthat 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 scientistswith 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
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.
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.