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Does Damage to Myelin-Producing Cells Trigger Nervous System Inflammation?

December 14, 2015

New Evidence for This Possibility from a Mouse Study by National MS Society-Funded Researchers

  • A collaborative team funded in part by the National MS Society reports on a new mouse model that mimics aspects of progressive MS. This model may be useful as a new tool for testing therapies designed to protect the nervous system and stop progression of disease.
  • The mouse model is characterized by widespread loss of myelin-making cells, which is followed by a much later immune attack on the brain and spinal cord and MS-like neurological symptoms.
  • This finding offers some support for the alternative idea of what initiates MS: rather than the immune attack in MS causing myelin damage and the loss of myelin-making cells, the reverse may happen, with damage or abnormalities to myelin and myelin-making cells triggering immune attacks and inflammation. 
  • The team (led by Brian Popko, PhD, of the University of Chicago, and co-investigator Stephen Miller, PhD, of Northwestern University) has published results in Nature Neuroscience (early online publication, December 14, 2015).

Background: MS has traditionally been thought to be an “outside-in” process, launched by immune cells that invade the brain and spinal cord and attack and destroy myelin, the material that surrounds and protects nerve fibers. The cells that make myelin (oligodendrocytes) are also damaged and destroyed. However, recent evidence from brain samples of people with MS suggests the possibility of an “inside-out” process: that myelin and oligodendrocyte damage or abnormalities may sometimes occur first, which then trigger an immune response against myelin. Understanding the underlying chain of events and mechanisms leading to MS and MS progression will help researchers identify critical pathways that could be targeted by new therapies aimed at stopping MS and restoring function.
Brian Popko, PhD (University of Chicago),  Stephen Miller, PhD (Northwestern University) and colleagues have developed mice that have been genetically modified so that their oligodendrocytes can be accessed and destroyed in a controlled way.
The Study: The team created a novel mouse model in which the myelin-producing oligodendrocytes are selectively destroyed via injection of a toxin inducing agent. The mice develop neurological disability that resolves in about 10 weeks, after the myelin is naturally repaired by new oligodendrocytes. However, new neurological deficits arise after about 30 weeks, and these symptoms are driven by the infiltration of immune cells attacking myelin. The team was able to stop disease progression at this late stage by turning off the myelin-specific immune responses.
Taken together, this laboratory study offers some support for the inside-out hypothesis of MS initiation, and also suggests that this mouse model may have potential as an important new tool for testing therapies designed to protect the nervous system and stop progression of disease.
The collaborative team has published results in Nature Neuroscience (early online publication, December 14, 2015).
This study was funded in part by the National MS Society, with special funds from the Illinois Lottery.
Read more about recent research progress in MS
Read more about research on progressive MS

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.


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