Breaking News
Researchers Report Success Promoting Myelin Repair in Mice with MS-like Disease
October 5, 2007
Courtesy NationalMSSociety.orgResearchers report that blocking or removing a myelin molecule called “LINGO-1” promotes myelin repair and enhances nerve fiber integrity in the spinal cords of mice with the MS-like disease EAE. Myelin is the insulating sheath that encases nerve fibers and is a main target of the destructive immune attack in multiple sclerosis. Sha Mi, PhD (Biogen Idec, Inc., Cambridge, MA) and colleagues report their findings in Nature Medicine (Advance Online Publication, September 30, 2007). The study was funded by Biogen Idec Inc.
The team had reported the discovery of LINGO-1 in 2004 (Nature Neuroscience, March 2004). LINGO-1 is part of a complex of molecules within myelin called the Nogo receptor complex that has been shown to inhibit the regeneration of nerve fibers. When LINGO-1 was disabled within this complex, remyelination occurred and the health of nerve fibers improved, leading the team to realize that LINGO-1 plays a crucial role.
In the current study, Dr. Mi and colleagues first induced EAE in mice with and without the gene that instructs production of LINGO-1. Both groups developed EAE symptoms, but they were significantly milder in mice lacking LINGO-1. Studies of tissue samples showed significant amounts of myelin repair in these mice as well. The team then administered a LINGO-1 antibody capable of blocking its activity to mice that already had symptoms of EAE and found that treatment stabilized disease progression after two weeks. Tissue analysis showed that blocking LINGO-1 reduced nerve fiber damage and enhanced myelin repair in the spinal cord, compared with untreated mice.
These pre-clinical results indicate that blocking LINGO-1 may have therapeutic potential for enhancing tissue repair in MS, but further research is necessary to determine safety and effectiveness. According to a company press release dated September 30, 2007. Biogen Idec Inc. plans to continue to pursue further research on this new approach for treating MS.
-- Research and Clinical Programs Department
Advice for dealing with mild or "benign" MS
Written by: Doug Schell, ARNP, MSCN
Used with permission from MIDAMERICA NEUROSCIENCE INSTITUTE
New research published this month in the journal Neurology shows that people diagnosed with “benign” or mild multiple sclerosis should discuss their treatment options with an MS expert. A recent study followed 169 people who had mild courses of the disease for the first ten years after diagnosis. After twenty years, almost half of them had developed more severe disabilities and were no longer classified as “benign.” The study shows that it is impossible to know whether the disease will remain benign or will begin to become more active.
As we know at the Institute, "benign" MS can only be diagnosed in retrospect. Since we have no crystal ball to help us predict who will have mild or benign MS, or who will have severe or progressive MS, most patients with a definite diagnosis should be treated with medication, which is the best insurance to keep the disease mild or in remission.
Research information update: Treatment for progressive multiple sclerosis
Below is a summary of information on a compound that may offer hope for MS patients with secondary progressive MS. Preliminary information published from a limited, phase II research trial in humans (not just rats!) showed a delay in progression of disease compared to patients on placebo or no treatment. The drug is called MBP8298 with MBP standing for ‘myelin basic protein.’ Results of a larger research trial in Canada and Western Europe (a phase III trial) may be available in mid-2008. Written below are details in more technical language for those interested.
Keith Edwards, M.D. January 27, 2007
MAESTRO-01
Trial
The MAESTRO-01 pivotal phase II/III, multi-center, double-blind,
placebo-controlled trial is designed to evaluate the safety and efficacy
of MBP8298 in patients with secondary progressive MS. The study is being
conducted at 48 sites across Canada and Europe and will include
approximately 550 patients being administered either MBP8298 or placebo
intravenously every six months for a period of two years. The primary
clinical endpoint for the trial is defined as a statistically and
clinically significant increase in the time to progression of the
disease as measured by the Expanded Disability Status Scale (EDSS), in
patients with HLA-DR2 and/or HLA-DR4 immune response genes. Time to
disease progression in patients with other HLA-DR types will be assessed
separately as an exploratory arm of the same study.
To date the trial has successfully passed six safety reviews by its
independent Data Safety Monitoring Board.
About MBP8298 - Novel Mechanism of Action
In MS patients, the body's immune system inappropriately attacks the
myelin coating around the nerves in the brain and spinal column, whereas
healthy people are otherwise "tolerant" of such common body components.
The proposed mechanism of action of MBP8298 is, by design, to
re-introduce such a state of "tolerance" to a critical portion of the
nerve's Myelin Basic Protein that is an immunological site of attack in
many MS patients. This is accomplished by the I.V. injection of MBP8298
every six months.
Phase II and long-term follow-up treatment of MS patients with MBP8298,
recently published in the European Journal of Neurology showed that
MBP8298 safely delayed the median time to disease progression for five
years in progressive MS patients with HLA-DR2 or HLA-DR4 immune response
genes.
MBP8298 is being developed in three late-stage clinical trials:
-- MAESTRO-01: A pivotal phase III trial in Canada and Western Europe
evaluating MBP8298 for the treatment of secondary progressive multiple
sclerosis (SPMS). The trial is a randomized, double-blind study of
approximately 550 patients.
-- MAESTRO-03: A pivotal phase III U.S. trial evaluating MBP8298 for the
treatment of SPMS. The trial is a randomized, double-blind study
enrolling approximately 510 patients.
-- MINDSET-01: A phase II trial evaluating MBP8298 for the treatment of
relapsing remitting multiple sclerosis (RRMS). The trial is a
randomized, double-blind study enrolling up to 215 patients.
About Multiple Sclerosis
Multiple sclerosis (MS) is thought to affect as many as 2.5 million
people worldwide, including approximately 75,000 in Canada, 400,000 in
the United States and more than 500,000 in Western Europe. MS is a
progressive disease of the central nervous system, characterized
initially by episodes of paralysis, blindness, sensory disturbances and
cognitive impairment. Almost half of all MS patients have the secondary
progressive form of the disease.