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Researchers Funded By the National MS Society Shed New Light on Immune Attacks in MS and a Possible New Treatment Strategy

July 21, 2014

A team funded by the National MS Society has shed new light on immune cells known as macrophages, and how one type of these cells may play a significant role in launching damage in MS. The researchers have discovered a way to differentiate between good and bad types of these immune cells active during MS-like disease in mice, and if further research shows that these findings hold true for people with MS, this opens up possibilities for developing therapies that target the bad cells and spare the good cells. Richard Ransohoff, MD, Ryo Yamasaki, MD, PhD (Cleveland Clinic Foundation) and colleagues report their findings in The Journal of Experimental Medicine (published online July 7, 2014).

Background: MS is known to involve immune system attacks against the brain and spinal cord, damaging the myelin that surrounds and protects nerve fibers, as well as the nerve fibers themselves. The sequence of events and immune cells involved in this damage are not completely clear. In an MS-like disease model called EAE, immune cells known as macrophages (macro, meaning “big,” and  phages, meaning “ eaters”) play a dominant role in the immune attacks and their numbers increase with the severity of the disease in mice. The mechanisms by which macrophages promote EAE are not entirely clear, but might involve “eating” myelin from nerve cells.

Some macrophages are derived from cells within the brain (called microglia) and some are derived from cells known as monocytes which enter from the bloodstream, and they are thought to have different roles. To date, no research techniques have permitted researchers to differentiate between these two different types of macrophages and their roles in the disease process.

The Study: Dr. Ransohoff’s team developed a novel strategy to label these two types of macrophages and differentiate their activities, including the use of a novel microscopy method that generates high resolution 3D images from small samples.

The team found that macrophages derived from monocytes initiated damage to myelin immediately upon the onset of EAE in mice. These cells also attached themselves to the nodes of Ranvier – specialized structures along nerve fibers that are crucial to proper nerve impulse conduction. Abnormalities in these nodes have been noted in people with MS, and the authors suggest that these findings may help to explain these abnormalities. Macrophages derived from microglia did not cause damage or attach to nodes, but rather seemed to be involved in the helpful process of clearing debris from the damage site.

The team conducted a series of other studies to understand the different roles of macrophages, which supported these findings.

Conclusion: This study provides important and novel insight into the early stages of the immune attack in a mouse model of MS. If there are both good (debris-clearing) and bad (myelin-destroying) macrophages in people with MS, strategies for inhibiting the bad macrophages and promoting the good macrophages could be beneficial for people living with MS.

Read more about how the National MS Society is funding research to stop the immune attack in its tracks in people with 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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