Chronic inflammation in multiple sclerosis could finally be defeated
[Mar. 16, 2023: Josh Barney, University of Virginia Health System]
Findings give researchers a prime target in their efforts to develop new treatments for multiple sclerosis and other autoimmune diseases. (CREDIT: Creative Commons)
UVA Health neuroscientists have discovered a potential way to disrupt the chronic inflammation responsible for multiple sclerosis.
UVA’s new study identifies 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 multiple sclerosis and other autoimmune diseases.
The research was 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).
“We are approaching the search for multiple sclerosis 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.”
Inflammation in Multiple Sclerosis
Multiple sclerosis affects nearly a million Americans. Symptoms can include muscle spasms, stiffness, weakness, difficulty moving, depression, pain and more. There is no cure, so treatments focus on helping patients manage their symptoms, control flareups and slow the progression of the disease.
Scientists have struggled to understand the causes of MS, but 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.
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.
Andrea Merchak, a doctoral candidate in neuroscience, led the research for Alban Gaultier of the School of Medicine’s Department of Neuroscience and its Center for Brain Immunology and Glia, or BIG.
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.
Ultimately, though, UVA’s new research lays an important foundation for future efforts to target the microbiome to reduce the inflammation responsible for multiple sclerosis and other autoimmune diseases.
“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.”
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.
Symptoms of Multiple Sclerosis
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:
Numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk
Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign)
Tremor, lack of coordination or unsteady gait
Vision problems are also common, including:
Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement
Prolonged double vision
Multiple sclerosis symptoms may also include:
Tingling or pain in parts of your body
Problems with sexual, bowel and bladder function
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Note: Materials provided above by University of Virginia Health System. Content may be edited for style and length.
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