Microbiome may play a role in development of multiple sclerosis, study finds

17 Oct 2018 --- Gastrointestinal microbiota could play a far greater role in the pathogenesis of multiple sclerosis (MS), researchers at the University of Zurich have identified. The study noted that immune cells that are activated in the intestine migrate to the brain, where they may cause an “inflammatory cascade.” The researchers suggest that it is worth broadening the research perspective to gain a better understanding of the pathological processes.

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.

Inflammatory cascade
Published in Science Translational Medicine, 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 who have 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, Clinical Research Priority Program Multiple Sclerosis, University of Zurich.

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.

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.

“Our clinical approach specifically targets the pathological autoreactive immune cells,” she says. 

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.

The clinical approach of the research group 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. This therapeutic approach aims for effective targeted treatment without severe side effects.