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.
$3.8 million (out of a total of $15.6 million for the Repair and Protection
Robin J. M. Franklin, PhD, DVM
University of Cambridge, Cambridge, UK
San Raffaele Hospital, Milan, Italy
Catherine Lubetzki, MD, PhD
Jean-Léon Thomas, PhD
Bruno Stankoff, MD
Hôpital de la Salpetrière, Paris
Brahim Nait-Oumesmar PhD
INSERM U546, Paris
Goldman, MD, PhD
Benjamin Segal, MD
Fraser Sim, PhD
University of Rochester, New York
Montreal Neurological Institute, Quebec, Canada
University of Calgary, Alberta, Canada
David H. Rowitch,
Dana-Farber Cancer Institute, Boston, MA
Restoring myelin by identifying and amplifying natural repair factors
in the brain and by attempting transplantation of replacement cells.
In the early stages of multiple sclerosisalso known as relapsing-remitting
MSepisodes of numbness, poor balance, impaired vision, or other
neurological symptoms, are short-lived and are often followed by a full
recovery. At this stage, some repair of the myelin coating that insulates
wire-like nerve fibers does occur, leading to remission. As the disease
progresses, however, myelin repair falls short and nerve fibers are exposed
to damage as well, leading to progressive disability. Searching for ways
to boost these early myelin repair capabilities is an important and exciting
frontier in MS research.
PhD, FRCP, is a Professor of Neurological Genetics and a principle investigator
of the Cambridge Center for Myelin Repair, funded by the MS Society of
Great Britain and Northern Ireland. He is a leading expert in the biology
of oligodendrocytes, the cells that make myelin. Now, with funding from
the U.S. National MS Society's "Promise 2010" Campaign, he is
leading an international team in an exploration of how to enhance the
body's myelin repair abilities by focusing on the biology and development
of the oligodendrocyte. This is Professor ffrench-Constant's first research
grant from the National MS Society.
First, Professor ffrench-Constant
and colleagues are attempting to find key molecules that promote myelin
repair. Previous studies have explored nutrients or growth factors that
may enable repair from outside oligodendrocytes, but this project is exploring
novel ground, as it will also focus on the critical molecules within
cells that may activate genes involved in myelin formation. Manipulating
these genes may offer a new route to promoting repair.
In their second aim,
this team is examining the use of neurospheres, immature nerve cells,
which have been shown to promote myelin repair in mice. Professor ffrench-Constant's
team is analyzing the mechanisms that these cells use to move from the
blood to the brain to promote repair. They are using magnetic resonance
imaging and electrical measurements of nerve conduction to examine the
effectiveness of this technique in animal models, with an eye toward improving
this novel therapy to the point that it could be used to treat people
To accomplish these
goals, Professor ffrench-Constant has assembled a "dream team"
of basic and clinical investigators who are experts in the fields of oligodendrocytes,
myelin, neurospheres, neuroimmunology, the genetics of oligodendrocyte
development, and models of myelin damage/repair. The collaboration spans
Canada, France, Italy, the United Kingdom and the United States.
"We are trying
to develop new drugs that enhance myelin repair by finding the key molecules
that promote this process," Professor ffrench-Constant explains.
"By manipulating these molecules, we should be able to promote repair.
We also will see if myelin repair can be enhanced by using cell transplants
to provide new cells."
This team is poised
to break new ground in their examination of the cells and molecules that
promote myelin repair, and their findings may yield new strategies to
the therapeutic armamentarium in 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.