A team of researchers at Weill Cornell Medical College in New York City reported this week on additional findings related to epsilon toxin and multiple sclerosis. Epsilon toxin is produced by a specific strain of bacteria (Clostridium Perfringens), and the team had previously reported evidence of this toxin in a woman newly diagnosed with MS and that about 10% of people with MS showed signs of having been exposed to the toxin. Their new study reports effects of the toxin in mice, where it can cause nervous system damage similar to that seen in MS. Further study is needed to prove that this toxin can trigger MS. These studies are proceeding with National MS Society funding to team leader Timothy Vartanian, MD, PhD.



Background: The cause of MS is still unknown. However, several factors suggest that an infectious agent or agents may be involved in triggering MS in susceptible individuals. (Read more) To date, researchers have not been able to identify a single infectious trigger for MS. It is important to note that MS is not contagious.



Multiple steps are required in order to show that a particular trigger causes MS. Researchers must prove that: the trigger is in the body before MS develops, and that the trigger actually causes the disease and is not just happening alongside the disease.



Studies: In October 2013, Dr. Vartanian’s team reported that they had detected a toxic bacterium called Clostridium Perfringens Type B in a woman who had exhibited the first symptoms of MS just three months before. This type of bacteria is closely related to those that cause foodborne illness. The team then examined serum and spinal fluid banked from people with MS and people without MS, and found, based on signs of immune reactions, that 10% of those with MS showed signs of previous exposure to the toxin, versus 1% of the healthy controls. (PLoS One. 2013 Oct 16;8(10):e76359) The team noted that levels were probably underestimated, since the immune reaction to this toxin dissipates over time.



More recently, Jennifer Linden, PhD, of the Weill Cornell team presented further findings this week at the American Society of Microbiology Biodefense and Emerging Diseases Research Meeting in Washington D.C. (Abstract 067 B)

The team studied which cells were targeted by a specific strain of C. Perfringens in mice (not the strain involved in foodborne illness). They found that epsilon toxin could kill oligodendrocytes (the cells that make myelin, the substance that surrounds nerve fibers and is a main target of the immune attack in MS), and that long-term exposure to the toxin reduced both these cells and myelin proteins. The toxin also affected the meninges, which are membranes that surround the brain and are sites of inflammation in people with MS. Treating mice with antibodies that neutralize C. Perfringens inhibited the loss of oligodendrocytes and myelin.



The team also tested samples of foods from local grocery stores for the presence of C. perfringens and the gene that instructs the toxin. Of 37 food samples, 13.5% were positive for the bacterium and about 3% were positive for the epsilon toxin gene. It is important to note that there is no evidence for any connection between food contamination and multiple sclerosis.



Conclusion: This team presents exciting preliminary findings on a possible trigger for MS. More research is necessary to show that this toxin may actually trigger the disease in people, and to provide evidence that contaminated food is a culprit for transmitting the toxin to people who develop MS.



In its effort to pursue all promising paths to uncover solutions for everyone with MS, the National MS Society has committed to funding Dr. Vartanian’s team. The research project will focus on analyzing exposure to epsilon toxin in a larger sample of people with MS and healthy controls. This study should provide vital information to help determine whether epsilon toxin is a trigger for MS, and whether this trigger can be stopped or prevented.