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National MS Society-Funded Study Shows Diabetes Drug Improves Mice with MS-Like Disease

Researchers funded in part by the National MS Society reported that metformin, an oral drug used to treat diabetes, improved MS-like disease in mice. Narender Nath, PhD (Medical University of South Carolina, Charleston) Shailendra Giri, PhD (Mayo Clinic, Rochester, MN) and colleagues report this study in The Journal of Immunology (2009 Jun 15;182[12]:8005-14). Dr. Giri was funded by Society research grants.

Background: In the immune attack that occurs in multiple sclerosis, inflammatory molecules secreted by immune cells damage tissue in the brain and spinal cord. AMPK is an enzyme that plays a role in providing cells with energy. With seed money from a Society pilot research grant, results of which were leveraged to win a larger research grant, Dr. Giri’s team has been studying whether this enzyme affects immune cells in lab mice with EAE, an MS-like disease. They recently reported that AMPK is, in fact, absent during EAE in another Society-supported study (Biochemical and Biophysical Research Communications 2009;386:16-20). Metformin, an oral drug commonly used to treat diabetes, activates AMPK, so they tested whether administering this agent would affect EAE.

The Study: The group administered metformin to mice both before and after disease onset. Treatment showed benefits in both models, delaying disease onset and reducing disease severity in the former, and increasing the rate of recovery in the latter. Metformin inhibited a number of immune messenger proteins, as well as the ability of immune cells to enter the brain. The team found evidence that these effects occurred because metformin activated AMPK in the brain and in immune scavenger cells known as macrophages.

Comment: “The fact that this oral drug, which has a long history of use in the treatment of diabetes, showed some benefit in EAE lends promise to our search for treatments that are relatively inexpensive and that already have a reasonably good safety profile,” said John R. Richert, MD, Executive Vice President of Research & Clinical Programs for the National MS Society. “Clearly, more research is necessary to determine whether this treatment will be a good therapeutic option for people with MS.”