The multiple sclerosis (MS) It is a disease that affects the nervous system and whose causes are unknown, although genetic predisposition is considered a risk factor that contributes to its appearance in the presence of certain environmental conditions. Every year around 1,800 new cases of MS are diagnosed in Spain –70% in people between 20 and 40 years old–, according to data from the Spanish Society of Neurology (SEN) and it is considered the second cause of acquired disability in young people, after traffic accidents.
New research has revealed that the bacteria intestinal Clostridium perfringenswhich produces the epsilon toxinis found in large quantities in the gut microbiome of patients with multiple sclerosis. In addition, in a preclinical model of MS, it was found that the epsilon toxin opened the blood vessels of the brain, facilitating the access of inflammatory cells to the central nervous system where they destroyed myelin, a lipoprotein that allows the transmission of impulses through neurons. .
The study was led by researchers from Weill Cornell Medicine and NewYork-Presbyterian and its results, which have been published in The Journal of Clinical Investigationsuggest that this bacterium may be responsible for triggering multiple sclerosis and also the progression of the disease.
“A treatment that neutralizes the epsilon toxin may stop the activity of multiple sclerosis more effectively than current treatments that suppress or modulate the immune system.”
“There are many mysteries in MS,” said co-senior author Dr. Timothy Vartanian, professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. “Why do some people get MS and others don’t, despite similar or identical genetics? What accounts for the episodic nature of relapses and remissions? How is the central nervous system attacked and why specifically myelin? Clostridium perfringens and epsilon toxin may explain many of these mysteries.”
Potential applications in the treatment of multiple sclerosis
For a person genetically susceptible to multiple sclerosis to develop the disease, they need to be exposed to an environmental trigger and an abundance of Clostridium perfringens in MS patients suggests that this bacterium could be the culprit. The strains of Clostridium perfringens that produce the epsilon toxin are found in the small intestine, and this toxin is only produced briefly when the bacterium is in a growth phase, consistent with MS which is in most cases characterized by a worm-shaped course. outbreaks (relapsing-remitting). Most notably, the epsilon toxin specifically targets brain blood vessels and myelin, which is a clear mechanism of its action.
Yinghua Ma, a research assistant professor of neuroscience in the Vartanian laboratory, used highly sensitive DNA detection techniques and found that people with multiple sclerosis are more likely to have C. perfringens that produces the epsilon toxin in the small intestine than the healthy individuals studied.
To test whether the toxin was capable of causing disease, they used a standard mouse model of multiple sclerosis in which animals are predisposed to autoimmunity, but MS-like disease only occurs if they also receive pertussis toxin. . Ma substituted pertussis toxin for epsilon toxin, and the mice developed a more MS-like disease compared to previous models.
“The finding that epsilon toxin can replace pertussis toxin in a mouse model of MS not only advances a more relevant model for studying MS, but critically defines a new microbially-derived determinant that causes a privilege break. immune response in the central nervous system to initiate the demyelinating disease,” explained Gregory F. Sonnenberg, Henry R. Erle Associate Professor of Medicine, MD-Roberts Family and co-author of the study.
“Epsilon toxin works at the earliest stage of MS lesion formation,” Vartanian said. “A treatment that neutralizes the epsilon toxin can stop new disease activity in our patients more effectively than current treatment modalities that suppress or modulate the immune system.” “In the immediate term, we are driven by a sense of urgency to obtain safer and more effective therapies for people with MS”, he concludes.