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Researchers Report Promising New Approach to Protecting the Nervous System from MS Damage

February 23, 2015

Collaborating researchers funded in part by the National MS Society through Fast Forward report promising early lab results from a new class of pharmaceutical compounds which have potential for both protecting the nervous system and turning off immune attacks. Further research is needed before these compounds can be tested for safety and benefits in people with MS. The paper, by Drs. Jeffery Haines, Patrizia Casaccia (Icahn School of Medicine at Mount Sinai, New York) and collaborators, was published early online on February 23, 2015 in Nature Neuroscience.

Background: Multiple sclerosis involves immune attacks on tissues in the brain and spinal cord, also called the central nervous system. Damage to nerve-insulating myelin and to the nerve fibers themselves interferes with the transmission of nerve signals. Current therapies reduce the force and number of immune attacks but no therapy yet can completely stop or reverse the damage or the progression of symptoms.

Dr. Casaccia and colleagues have been investigating the potential role that abnormal transport of proteins within cells may play in the damage to nerve fibers that occurs in MS. Previous research suggested that a protein called CRM1 moves or exports materials from within the cell nucleus to the body of the cell, and these abnormal exports have been linked to cell damage. This research team found CRM1 to be active in damaged nerve fibers in the brains of people with MS.

With this in mind, they wanted to see whether blocking CRM1 with newly discovered compounds could reduce nerve damage in several laboratory models of MS. This study was made possible by several funders including the National Institutes of Health, the National MS Society through a Fast Forward seed grant, and Karyopharm Therapeutics, a company developing the pharmaceutical CRM1 inhibitors, called KPT-276 and KPT-350, tested in this study.

The Study: The researchers conducted a series of tests to further understand the role of CRM1 in nerve fiber damage and to determine whether the inhibitors of CRM1 could reduce MS-like disease (EAE) in mice and show potential in other ways for protecting the nervous system from damage.

They found that giving oral doses of the CRM1 inhibitors to mice that had leg paralysis from EAE could decrease disease severity and protect the mice from disease progression and nerve damage. They also reported that the CRM1 inhibitors could reduce the inflammation which is characteristic of EAE and also a feature of human MS.

Comment: "The fact that inhibition of CRM1 led to both a decrease in neuroinflammation and a direct neuroprotective effect is intriguing," said Mark Allegretta, PhD, the National MS Society's Associate Vice President, Commercial Research, the division that provided funding to Karyopharm Therapeutics and Dr. Casaccia for this work. "The data indicate that KPT compounds provide neuroprotection by targeting multiple causes of nerve damage." If these positive results hold up with further research, and the compound proves safe and beneficial in future clinical trials involving people with MS, it could mean a new approach that could potentially slow MS progression and disease activity.

Read more about the Society's investments to drive commercial research.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.

About the National Multiple Sclerosis Society

The National MS Society, founded in 1946, is the global leader of a growing movement dedicated to creating a world free of MS. The Society funds cutting-edge research for a cure, drives change through advocacy and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, X, formerly known as Twitter, Instagram, YouTube or 1-800-344-4867.

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