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Drugs currently used to treat Type 2 diabetes may also prove useful for treatment of multiple sclerosis, according to studies at the University of Illinois at Chicago and the West Side Veterans Administration Hospital. The results are published in the June issue of the journal Annals of Neurology. Douglas Feinstein, a research associate professor of anesthesiology at UIC, says two antidiabetic drugs called thiazolidinediones, or TZDs, already approved by the Food and Drug Administration for treatment of Type 2 diabetes, prevented the development of an animal model of MS in the studies.
Other tests, already under way, are designed to test if the drugs could also be effective in other neurologic diseases, including Alzheimer's, Parkinson's and stroke, he says.
The drugs prevented the MS-like disease known as experimental autoimmune encephalomyelitis from occurring in healthy mice and reduced symptoms when given to mice that were already ill. Moreover, the drugs were effective in two different models of the disease, a chronic form in which the mice became ill and remained sick and a model in which the mice developed a relapsing form of the disease, which is similar to the more prevalent form of MS.
The antidiabetic TZDs used in the study were originally developed to increase the body's sensitivity to the low levels of insulin present in Type 2 diabetes. Rather than influencing the amount of insulin in the body, these insulin-sensitizing drugs increase the ability of cells and tissue to take up the correct amount of glucose, Feinstein explains.
However, more recent studies demonstrate that the drugs carry out other actions, he says. The drugs prevent the activation and growth of lymphocytes and reduce the production of inflammatory substances by activated brain cells. He and his colleagues believe this may be the primary way the drugs act to reduce the symptoms of MS in mice.
MS is believed to result from increased production of inflammatory immune proteins. This immune activity causes damage to myelin, the substance that insulates nerve fibers, along with nerve fibers themselves.
"The causes of MS are not completely understood," Feinstein says. "However, it is known that activated lymphocytes in the bloodstream enter the brain, where they produce toxic substances that eventually cause damage to the myelin-forming cells of the brain [the oligodendrocytes] and to neurons as well. In addition, once in the brain, the lymphocytes activate resident brain cells that further increase the production of toxic substances."
Feinstein is now designing a clinical trial to test the safety and proper dosage of the drugs in MS patients. He hopes to start that trial within a year.
Even if the drugs are only as good as those currently in use, they still offer an advantage for patients because they can be taken orally.
"The minimum we're hoping for is that they will be as good as any of the existing drugs," Feinstein says. "But there's a possibility they could prove to be better because this is a different class of drugs with different targets and effects."
The study involved collaborations with researchers at several other universities and hospitals, including Dr. Michael Heneka of the University of Bonn in Germany, and was supported by a grant from the National Multiple Sclerosis Society.
[www.uic.edu ]
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Last Revised at December 10, 2007 by Lusine Kazoyan, M.D.
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