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10/10/2018

Link between gut flora and multiple sclerosis discovered

esclerosis_mireia_carmen

10/10/2018

Gastrointestinal microbiota could play a far greater role in the pathogenesis of the disease than previously assumed.

A study carried out by the University of Zurich, in which researchers from the Clinical Neuroimmunology group of the Vall d'Hebron Research Institute (VHIR) and the Multiple Sclerosis Center of Catalonia (Cemcat) have collaborated, has discovered that the gastrointestinal microbiota could play a role much greater role in the origin of multiple sclerosis than previously thought. The results are published today in Science Translational Medicine Journal.Multiple sclerosis is an autoimmune disease in which the body's own immune system attacks and damages the protective coating around nerve cells. This coating is made up of myelin - a biological membrane of protein and fatty substances - which is why research efforts to find the disease's target antigen have so far focused on the myelin membrane's components.New findings made by the research group of Mireia Sospedra and Roland Martin from the University of Zurich's Clinical Research Priority Program Multiple Sclerosis now suggest that it is worth broadening the research perspective to gain a better understanding of the pathological processes.Inflammatory cascadeIn thi study, the scientists report that T cells - i.e. the immune cells responsible for pathological processes - react to a protein called GDP-L-fucose synthase. This enzyme is formed in human cells as well as in bacteria frequently found in the gastrointestinal flora of patients suffering from multiple sclerosis. "We believe that the immune cells are activated in the intestine and then migrate to the brain, where they cause an inflammatory cascade when they come across the human variant of their target antigen," says Mireia Sospedra.From the VHIR and Cemcat, doctors Carmen Espejo and Herena Eixarch have contributed to the study with the determination of the encephalitogenic capacity of GDP-L-fucose synthase in experimental models of multiple sclerosis, in particular, experimental autoimmune encephalomyelitis, in the who have extensive and recognized experience.For the genetically defined subgroup of MS patients examined by the researchers, results show that gut microbiota could play a far greater role in the pathogenesis of the disease than previously assumed. Mireia Sospedra hopes that these findings can soon also be translated into therapy, she plans to test the immunoactive components of GDP-L-fucose synthase using an approach that the researchers have been pursuing for several years already.Re-educating the immune systemThis approach involves drawing blood from MS patients in a clinical trial and then attaching the immunoactive protein fragments onto the surface of red blood cells in a laboratory. When the blood is reintroduced into the bloodstream of patients, the fragments help to "re-educate" their immune system and make it "tolerate" its own brain tissue. "Our approach specifically targets the pathological autoreactive immune cells," says Sospedra. In this sense, another of the authors of the study, Dr. Carmen Espejo, principal investigator of the Clinical Neuroimmunology group at VHIR and the Multiple Sclerosis Center of Catalonia (Cemcat), insists on "the importance of this finding for the development of specific antigen therapies that allow the reeducation of the immune system and thereby avoid the attack on the structures of the central nervous system".This approach therefore differs radically from other treatments that are currently available, which throttle the whole immune system. While these treatments often succeed in stopping the progression of the disease, they also weaken the immune system - and can thus cause severe side effects.

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