Researchers develop life-changing treatment for multiple sclerosis

[Apr. 16, 2023: JD Shavit, The Brighter Side of News]

Multiple sclerosis (MS) is a debilitating autoimmune disease that affects nearly a million Americans. It causes muscle spasms, stiffness, weakness, difficulty moving, depression, pain, and other symptoms. There is no known cure for MS, and current treatments focus on managing symptoms, controlling flare-ups, and slowing the disease's progression. However, UVA Health neuroscientists have recently discovered a potential way to disrupt the chronic inflammation responsible for MS.

The new study, conducted by Andrea Merchak, a doctoral candidate in neuroscience, and her colleagues in the lab of Alban Gaultier, PhD, of the University of Virginia School of Medicine's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG), identified a vital contributor to the hyperactive autoimmune response and neuroinflammation that are the hallmarks of MS. Blocking this "lynchpin" in a research model of MS alleviated the harmful inflammation, giving researchers a prime target in their efforts to develop new treatments for MS and other autoimmune diseases.

"We are approaching the search for MS therapeutics from a new direction," Merchak said. "By modulating the microbiome [the collection of microorganisms that naturally live inside us], we are making inroads in understanding how the immune response can end up out of control in autoimmunity. We can use this information to find early interventions."

In recent years, scientists have struggled to understand the causes of MS. However, recent research suggests an important role for the gut microbiome. UVA's new findings bolster that, determining that an immune system controller found in "barrier tissues" such as the intestine plays a vital role in the disease. This regulator can reprogram the gut microbiome to promote harmful, chronic inflammation, the researchers found.

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Gaultier and his collaborators blocked the activity of the regulator, called "aryl hydrocarbon receptor," in immune cells called T cells and found that doing so had a dramatic effect on the production of bile acids and other metabolites in the microbiomes of lab mice. With this receptor out of commission, inflammation decreased, and the mice recovered.

The findings suggest that doctors may one day be able to take a similar approach to interrupt the harmful inflammation in people with MS, though that will take much more research. Before that can happen, scientists will need a much better understanding of the interactions between the immune system and the microbiome, the UVA researchers say.

"Due to the complexity of the gut flora, probiotics are difficult to use clinically. This receptor can easily be targeted with medications, so we may have found a more reliable route to promote a healthy gut microbiome," Merchak said. "Ultimately, fine-tuning the immune response using the microbiome could save patients from dealing with the harsh side effects of immunosuppressant drugs."

Multiple sclerosis is an autoimmune disease that affects the central nervous system, including the brain and spinal cord. It damages the protective covering of nerve cells, which leads to communication problems between the brain and the rest of the body.

Symptoms of MS can range from mild to severe and vary widely depending on the individual. Some people experience muscle weakness or spasticity, while others may have trouble with balance or coordination. Fatigue, numbness, and tingling sensations are also common.

While there are currently treatments available to manage MS symptoms, there is no cure for the disease. As a result, researchers are continually searching for new ways to combat MS and improve the lives of those affected by it.

Gaultier and his team are part of UVA's TransUniversity Microbiome Initiative, which serves as the central hub for the university's cutting-edge microbiome research. The initiative aims to expand our understanding of the microbiome to better treat and prevent disease.

Gaultier and his collaborators have published their findings in the scientific journal PLOS Biology. The research team consisted of Merchak, Hannah J. Cahill, Lucille C. Brown, Ryan M. Brown, Courtney Rivet-Noor, Rebecca M. Beiter, Erica R. Slogar, Deniz G. Olgun, and Gaultier. The researchers had no financial interest in the work.

According to the Mayo Clinic, multiple sclerosis signs and symptoms may differ greatly from person to person and over the course of the disease depending on the location of affected nerve fibers. Symptoms often affect movement, such as:

Vision problems are also common, including:

Multiple sclerosis symptoms may also include:

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