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.
$3.6 million (out of a total of $15.6 million for the Repair and Protection initiative).
Funded in part by the MS Society of Great Britain and Northern Ireland
|David Baker, PhD
Lara Diemel, PhD
University College London,
|Yuti Chernajovsky, PhD|
University of London, London, UK
Lawrence Steinman, MD
Stanford University, Palo Alto, CA
Attempting to turn cells into vehicles that will deliver repair molecules to sites of injury in the brain, and screening molecules for their protective properties as a prelude to clinical testing in persons with MS.
In multiple sclerosis, inflammation damages the myelin insulation that protects nerve fibers, and also can damage the nerve fibers themselves. This results in neurological symptoms that may remit early in the disease, but often progress over time. There are no treatments that effectively prevent the progression of MS, or restore neurological function. Gavin Giovannoni, MBBCh, PhD, is spearheading a project to develop and assess novel treatments for progressive MS, with funding from the National MS Society's "Promise 2010" Campaign. This is Dr. Giovannoni's first grant from the National MS Society.
Dr. Giovannoni's team is investigating the effects of numerous drugs that have been found protective of the nervous system. The team is testing these neuroprotective drugs, as individual compounds or in combinations, in animal models of progressive MS-like disease. They also are using these models to develop new ways of measuring whether neuroprotection has been achieved, for use in clinical trials in people with progressive MS.
"There is currently no effective therapy for the progressive stages of MS," says Dr. Giovannoni. "We are addressing this void with a project that is a well-balanced mix of innovative basic science research and practical clinical research."
The body has some nerve tissue repair capabilities, but these eventually fail in MS—possibly because the body's store of immature myelin-making cells is depleted in MS, or because there is a lack of certain proteins called "growth factors" that stimulate tissue repair. Dr. Giovannoni and colleagues are exploring both possibilities by transplanting immature cells into animals with MS-like disease, along with a specific "carrier" molecule that has been engineered to release growth factors at sites of damage.
In a crucial phase of this study, Dr. Giovannoni and colleagues are seeking to accurately quantify and monitor alterations in both myelin and nerve fibers that occur in a model of optic neuritis, an eye disorder that is often the first symptom of MS. In this model, inflammation of the optic nerve is a simpler representation of the more complex and dispersed damage that occurs in MS. The team is using technology that can identify thousands of proteins at once to examine this model. These studies may help them to develop markers of myelin or nerve fiber damage that could then be applied to monitoring nervous system tissues in MS.
Dr. Giovannoni leads a group of investigators that spans basic to clinical science. Many co-investigators have long-term records of commitment to MS research, and have been involved with bringing interventions from the laboratory to the clinic.
This outstanding group can advance a new understanding of what causes damage in MS, and can also bring to the fore new, noninvasive technologies to use in MS diagnosis and treatment. 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.