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Researchers Supported by the National MS Society Develop New Mouse Model of MS That May Offer New Clues to Treatment

November 7, 2016

Summary
  • National MS Society-funded researchers have established and studied a new mouse model that mimics aspects of MS, especially MS in people who do not benefit from treatment with interferon beta.
  • Results suggest that the new subtype of the MS-like EAE which is resistant to interferon beta, and perhaps MS, has distinct features and may be treatable by targeting specific molecules.
  • Being able to detect interferon resistance in people with MS would allow the selection of more appropriate therapies sooner.
  • The study, by Drs. Makoto Inoue (University of Illinois at Urbana-Champaign), Mari Shinohara (Duke University School of Medicine) and colleagues, was published early online on November 7, 2016 in Nature Neuroscience.
Details

Background: MS is an unpredictable disease that involves attacks on the brain and spinal cord by the person’s own immune system. There is currently no way to predict whether a person will respond to a particular therapy. Although many people with relapsing MS can be treated effectively with interferon beta (interferon beta-1a, peginterferon beta-1a, and interferon beta-1b), a proportion of people don’t benefit, and may be “interferon resistant.” The underlying biological reasons for interferon resistance are not clear; achieving a better understanding could lead to ways to predict an individual’s response to therapies and identify the best treatment option early in the course of the disease.
 
To look at the question of interferon resistance, the researchers focused on EAE in mice. EAE is a laboratory-induced disease that mimics some aspects of human MS, and is an important research tool for gaining insights into specific disease mechanisms.
 
The study: The researchers compared two variants of EAE in mice. The first type was the type commonly used in research, which is induced by weak immune activation. This type could be successfully treated with interferon-beta. The second type was a new approach, which was induced with a stronger immune activation that bypassed immune reactions typical in the more standard EAE. Mice with the second type showed more inflammation, resistance to interferon beta, and more damage to nerve fibers. They also showed involvement of two immune molecules: LTbR and CXCR2. The investigators also reported that they could improve the second type of EAE by blocking the activity of LTbR and CXCR2.
 
When the researchers examined blood cells obtained from people with MS, some people with interferon resistance had higher levels of LTbR and CXCR2, compared to people whose MS responded to interferon treatment.
 
The study, by Drs. Makoto Inoue (University of Illinois at Urbana-Champaign), Mari Shinohara (Duke University School of Medicine) and colleagues, was published early online on November 7, 2016 in Nature Neuroscience.

Next Steps: This new variation of EAE may serve as a new model that will help scientists explore the mechanisms underlying interferon resistance in EAE and in MS. Further research should determine whether elevated blood levels of LTbR and CXCR2 can serve as biomarkers of interferon resistance, at least in some people. Being able to detect interferon resistance would allow the selection of more appropriate therapies sooner. Finally, because blocking LTbR and CXCR2 improved MS-like disease in mice, these molecules may be targets for the future development of more effective therapies. 

Read more about Society-Funded Research

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. 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. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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