Diabetes Drug Metformin Reduces Clinical Severity of Myasthenia Gravis in Animal Study

Diabetes Drug Metformin Reduces Clinical Severity of Myasthenia Gravis in Animal Study

The diabetes drug metformin, which is largely safe and minimally toxic, can be of therapeutical value for myasthenia gravis, according to a study conducted using a mouse model of the disease.

The study, “Metformin attenuates autoimmune disease of the neuromotor system in animal models of myasthenia gravis,” was published recently in the journal International Immunopharmacology.

Myasthenia gravis (MG) is a chronic autoimmune disease, in which the immune system mistakenly attacks healthy tissue in the body.

The mechanisms that perpetuate the disease are directly related to the presence of specific autoantibodies (antibodies directed toward healthy tissue) produced by a type of immune cell known as B cells.

Several studies in experimental models of MG have indicated that the secretion of the pro-inflammatory molecule IL-17 by an immune cell type known as Th17 cells is involved in the process of B cells producing antibodies.

In contrast, regulatory T cells (Tregs), which are essential for the maintenance of immune tolerance toward healthy tissue, are defective in MG patients at regulating immune responses compared to healthy people.

That’s why the imbalance of Th17 cells and Tregs is considered to be the main driver in the immune-related issues of MG.

Metformin, the most commonly prescribed medicine for type 2 diabetes, has been shown to have anti-inflammatory effects.

Research suggests that metformin can regulate the immune system by adjusting T cell populations, which indicates that metformin can be used for treatment of immune-mediated diseases in clinic.

However, whether metformin has a therapeutic role in B cell-mediated disorders such as MG has not been shown.

Researchers conducted this study to investigate the therapeutic potential of metformin using a classic animal model of human MG — the experimental autoimmune myasthenia gravis (EAMG) rats.

First, researchers showed that oral administration of metformin diminished  the onset of EAMG, significantly reduced clinical severity of the disease, and led to a reduction in mortality.

Additionally, they showed this effect was accompanied by a considerable decrease in circulating autoantibody levels with no effect on blood glucose levels.

While metformin treatment showed little effect in inducing Tregs, the drug was found to inhibit Th17 cell differentiation (maturation) by increasing signaling through a cell pathway known as AMPK.

Interestingly, AMPK has been suggested to reduce T-cell-driven inflammation in MG.

“Our findings verified that metformin attenuated the clinical manifestations of EAMG by impeding AChR antibody secretion in the serum of EAMG animals and Th17 differentiation without affecting Tregs by activating the AMPK pathway,” the authors concluded.

“Metformin has already been known to be safe and minimally toxic in treating patients with various disorders. Our study supported that metformin might have novel therapeutic potential in the clinical treatment of MG and other autoantibody-mediated diseases,” they wrote.

 

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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