Further Evidence for Epsilon Toxin as MS Trigger

February 05, 2014

Further evidence that multiple sclerosis (MS) may be triggered by a bacterial toxin has been reported by researchers from Weill Cornell Medical College.

A team led by Jennifer Linden, PhD, presented research at last week's American Society for Microbiology's Biodefense and Emerging Diseases Research Meeting showing that epsilon toxin, which is produced by certain strains of the bacteria Clostridium perfringens, can kill myelin-producing cells.

Dr. Linden told Medscape Medical News that permeability of the blood–brain barrier and demyelination of neurons are defining characteristics of MS.

"It has previously been shown that epsilon toxin is associated with blood–brain barrier permeability, and that it binds to white matter in the brain — this is where the heavily myelinated areas are. Now we have shown that than this toxin kills oligodendrocytes — myelin-producing cells in the brain. This toxin specifically targets the same cells that are destroyed in MS. This gives further weight to our hypothesis that epsilon toxin may be causing MS."

For the study, the researchers used 2 types of culture system made from mice brains. In 1 scenario, different brain cells were separated out. When treated with the epsilon toxin, the oligodendrocyte cells died, but the other cell types were not affected.

In another culture system, sections of the brain were used to mimic more closely what actually happens in the brain. The researchers observed that the toxin caused a loss of myelin from the neurons.

The researchers also report that epsilon toxin binds to retinal vascular and meningeal cells, additional sites of MS-related inflammation.

They also screened 37 food samples from local grocery stores for C perfringens. They found 13.5% were positive for the bacteria and 2.7% were positive for the epsilon toxin gene. "This suggests that infection by the epsilon toxin producing bacteria may be acquired from contaminated food," the researchers conclude.

They add that more studies are needed to determine human susceptibility to both the toxin and toxin-producing bacteria, so methods of prevention and treatment can be developed.

Dr. Linden told Medscape Medical News that her group is now testing whether epsilon toxin causes mice to develop abnormality similar to MS. They are also developing a vaccine against the toxin. This would be used as a research tool to begin with to develop antibodies for use in detection of the toxin.

She explained: "We need stronger human data detecting not only the bacteria in MS patients but detecting the toxin itself. We have detected antibodies to the toxin showing that an individual has been exposed to the toxin, but it would be better if we detected the toxin itself. At present, we can't detect epsilon toxin once it gets into tissues.

"This may be possible with the use of an antibody so we could test autopsy brain samples taken from MS patients and try and detect the toxin in the MS lesions. That would help further validate our hypothesis that this toxin causes MS. We would also use the vaccine to test whether it could prevent MS in a mouse model. In addition, neutralizing antibodies produced by a vaccine may be a possible treatment."

2014 American Society for Microbiology Biodefense and Emerging Diseases Research Meeting. Presented January 28, 2014. Abstract 67B.

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