Multiple sclerosis: Damaged myelin not the trigger

February 27, 2012, University of Zurich

Damaged myelin in the brain and spinal cord does not cause the autoimmune disease multiple sclerosis (MS), neuroimmunologists from the University of Zurich have now demonstrated in collaboration with researchers from Berlin, Leipzig, Mainz and Munich. In the current issue of Nature Neuroscience, they therefore rule out a popular hypothesis on the origins of MS. The scientists are now primarily looking for the cause of the development of MS in the immune system instead of the central nervous system.

Millions of adults suffer from the multiple sclerosis (MS). It is relatively certain that MS is an autoimmune disease in which the body's own defense cells attack the myelin in the brain and spinal cord. Myelin enwraps the and is important for their function of transmitting stimuli as . There are numerous unconfirmed hypotheses on the development of MS, one of which has now been refuted by the neuroimmunologists in their current research: The death of , as the cells that produce the are called, does not trigger MS.

Neurodegenerative hypothesis obsolete

With their research, the scientists disprove the so-called "neurodegenerative hypothesis", which was based on observations that certain patients exhibited characteristic myelin damage without a discernable . In the popular hypothesis, the scientists assume that MS-triggering myelin damage occurs without the involvement of the immune system. In this scenario, the immune response against myelin would be the result – and not the cause – of this pathogenic process.

The aim of the research project was to confirm or disprove this hypothesis based on a new mouse model. Using genetic tricks, they induced myelin defects without alerting the immune defense. "At the beginning of our study, we found myelin damage that strongly resembled the previous observations in MS patients," explains Burkhard Becher, a professor at the University of Zurich. "However, not once were we able to observe an MS-like autoimmune disease." In order to ascertain whether an active immune defense causes the disease based on a combination of an infection and myelin damage, the researchers conducted a variety of further experiments – without success. "We were unable to detect an MS-like disease – no matter how intensely we stimulated the immune system," says Ari Waisman, a professor from the University Medical Center Mainz. "We therefore consider the neurodegenerative hypothesis obsolete."

Focus on immune system

The teams involved in the study want to continue researching the cause and origins of MS. "In light of these and other new findings, research on the pathogenesis of MS is bound to concentrate less on the brain and more on the immune system in future," says Professor Thorsten Buch from the Technischen Universität München.

Explore further: Neuroimmunologists find gut bacteria link to multiple sclerosis

More information: Giuseppe Locatelli, Simone Wörtge, Thorsten Buch, Barbara Ingold, Friederike Frommer, Bettina Sobottka, Martin Krueger, Khalad Karram, Claudia Bühlmann, Ingo Bechmann, Frank L. Heppner, Ari Waisman and Burkhard Becher. Primary oligodendrocyte death does not elicit anti-CNS immunity. Nature Neuroscience. February 26, 2012. Doi: 10.1038/nn.3062

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not rated yet Feb 27, 2012
It's my understanding that inflammation, not damaged myelin, is the primary degenerative mechanism associated with MS, and that it is the body's inflammatory response that underlies the progressive damage that we see occurring in the myelin sheathing.

In combination with attempts at identifying an individual's genetic susceptibility to the condition, I think that it's extremely important to explore a patient's historical physical injury profile, especially where childhood head and neck trauma (or electrocution) have been involved. While it's possible that several different viruses may act as MS "provocateurs", it's unlikely (imo) that any particular virus will be found at the root of disease.
not rated yet Feb 27, 2012
I'm not a medical professional, but there is a Dr. Wahls who promotes dietary approach to M.S. She is a researcher, no slouch, not a zany person. To me the connection to inflammation makes sense from this viewpoint, as there are foods that cause inflammatory response in people.
not rated yet Feb 27, 2012
Good point, wealthychef. Specific foods can potentially act as episodic triggers for inflammatory responses, though neurological impacts would be less likely than the expected effects upon the digestive tract. Still, neurotoxicity can vary wildly between individuals, so all such avenues must be considered in managing the disease through the long term.
not rated yet Feb 27, 2012
I am just an ordinary GP with an interest in this field. I dont think its quite that black & white. If you look at eosinophilic myelitis - which is likely to be more common than we appreciate (or could ever prove) it is both a reflection of the immune response and relative albeit mostly transient dysfunction of the CNS. The Japanese are doing most of the work on atopic myelitis (presumably the overt form of eosinophilic myelitis). It is mostly transient though in some cases prolonged (weeks to months) and there clearly must be a significant degree of myelin or neuronal damage in such cases. Atopic myelitis occurs in atopic individuals, often with fluctuating hyperIgE serology but tends to be infrequent, a little like shingles. Zoster is still the commonest known virus to trigger myelitis and tends to only occur in an individual infrequently as opposed to MS which tends to give frequent and substantially motor function disturbance. The MRI imaging can be similar with AM and MS.
not rated yet Feb 27, 2012
oligodendrocytes, as the cells that produce the myelin sheath are called

Myelin in the peripheral nervous system is made by Schwann cells, not oligodendrocytes.
not rated yet Feb 28, 2012
I though in CNS, oligodendrocytes are the cells that produce myelin to form myelin sheath. Schwann cells are responsbile for froming myelin sheath in PNS. Since they are talking about the myelin in the brain and spinal cord, they are talking about the CNS and therefore it seems to me that there is nothing wrong with the statement "oligodendrocytes, as the cells that produce the myelin sheath are called".

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