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(NMSS)-Supported Investigators Uncover Clue to MS Relapses

December 4, 2006

Stanford University researchers have uncovered evidence they believe may explain the role of a protein in the repeated relapses of symptoms experienced by many people with multiple sclerosis, in which the immune system attacks the body’s own brain and spinal cord tissues.

The study, published early online in the journal Nature Immunology, was funded by the National MS Society, the National Institutes of Health and others.

Drs. Lawrence Steinman, Eun Mi Hur and colleagues identified the culprit protein as osteopontin, which previous studies had shown to be elevated in damaged areas (lesions) of the nervous system of people with MS and to show up in increased levels in the blood plasma prior to the onset of relapses in people with MS. Osteopontin has many different jobs in the body, such as the maintenance of bones, and has also been linked to other immune diseases including rheumatoid arthritis and lupus erythematosus.

The investigators worked with various mouse models of MS, and in mice that had normal levels of osteopontin versus those that were engineered to lack the protein. In a series of experiments, the team found that osteopontin could stimulate repeated relapses and enhance disease progression, and inhibit spontaneous recovery from symptoms. This resulted in much more severe disease than in those with normal levels of the protein.

When the immune system is doing its normal job, such as fighting off a viral infection, the immune cells that are activated to launch the attack eventually die off when the infection has been neutralized. In researching how osteopontin inhibited normal recovery from symptoms, Dr. Steinman’s team found that the protein enhanced the survival of activated immune cells. The team also identified several specific mechanisms through which this protein inhibited their usual elimination from the system.

This research may lead to new therapeutic approaches that target osteopontin. However, because this protein has multiple functions in the body, additional research should help pinpoint ways to inhibit its influence on the immune attack without altering its ability to do other jobs in the body.

http://www.nationalmssociety.org/research-2006Dec4.asp
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Protein Linked to MS Relapse

Daniel DeNoon
WebMD Health News 2006.

Dec. 4, 2006 -- A protein abundant in multiple sclerosis patients during disease flare-ups may be a key culprit in this and other autoimmune diseases.

The protein is called osteopontin. Several years ago, Stanford researcher Lawrence Steinman, MD, and colleagues found abnormally high osteopontin levels in parts of the brain affected by MS flare-ups.

Now Steinman and colleagues find that in three different mouse models of MS, osteopontin causes disease relapse and makes disease symptoms worse.

The reason: osteopontin protects immune cells that have gone haywire and attack the brain. Normal protective mechanisms trigger self-destruction in aberrant immune cells. But osteopontin stops this signal, prolonging the lives of these cells.

Steinman's team is working on antibodies to block osteopontin. But Steinman admits there may be a problem with this approach. Osteopontin seems to play a major role in many normal body functions.

"Like a lot of important biological molecules, osteopontin has a Janus-like quality -- a bad side and a good side," Steinman says in a news release. "We're going to be extremely lucky if we give the antibody opposing osteopontin and derive just the good side."

The new findings appear in the Dec. 3 advance online edition of Nature Immunology.

SOURCES: Hur, E. Nature Immunology, advance online edition, Dec. 3, 2006. News release, Stanford University

http://www.webmd.com/content/article/130/117693


(Thanks Agate!)

Cherie