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.
Total Posts: 24
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.
×
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.
Latest Posts
  • metformin
  • Muscle weakness
  • Thymectomy
  • myasthenic crisis

3 comments

  1. Connie Pachek says:

    I have taken Metformin for years for my type 2 diabetes; and I still developed MG a year ago. Not sure Metformin helps in humans as it did in the lab experiments with animals.

  2. Douglas Monson says:

    I have MG and Diabetes type 2 and my MG is relatively mild compared to when it first flared up. I have been on Metaformin the entire time. I have noticed that the more controlled my blood sugar is, the less severe and frequent my MG flare ups. A lot of factors involved but I think it’s interesting the two are connected. Maybe largely because of the reduction in inflammation. More research please! Not much research going on for MG.

    • Thomas Cox says:

      I was diagnosed with MG at 60 yrs of age. I’m now 68 and symptoms are in remission since starting on Cellcept (mycophenolate) when I turned 62. The drug is normally used to treat organ tansplant. I take 1,500mg twice a day. I have been using Metformin for three years but I don’t attribute it to MG improvement.

Leave a Comment

Your email address will not be published. Required fields are marked *