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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
Professor Charles ffrench-Constant Charles ffrench-Constant, PhD, FRCP
University of Cambridge
Cambridge, UK

$3.8 million (out of a total of $15.6 million for the Repair and Protection initiative)

Research Team  
Robin J. M. Franklin, PhD, DVM
University of Cambridge, Cambridge, UK

Gianvito Martino, MD
San Raffaele Hospital, Milan, Italy

Bernard Zalc, MD, PhD
Catherine Lubetzki, MD, PhD
Jean-Léon Thomas, PhD
Bruno Stankoff, MD
Hôpital de la Salpetrière, Paris

Annic Baron Van-Evercooren PhD
Brahim Nait-Oumesmar PhD
INSERM U546, Paris

Steven Goldman, MD, PhD
Benjamin Segal, MD
Fraser Sim, PhD
University of Rochester, New York

Jack Antel, MD
Montreal Neurological Institute, Quebec, Canada

Samuel Weiss, PhD
University of Calgary, Alberta, Canada

David H. Rowitch, MD, PhD
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 sclerosis—also known as relapsing-remitting MS—episodes 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.

Charles ffrench-Constant, 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 with MS.

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.

  Last updated August 5, 2005