Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) in which white blood cells known as lymphocytes attack the myelin insulation on nerves in the spinal cord and brain. Glatiramer acetate (GA) is a drug currently approved for MS treatment, but new therapies are needed to improve effectiveness and reduce side effects. Now, in a study appearing online on March 16 in advance of print publication in the April issue of the Journal of Clinical Investigation, Scott S. Zamvil and colleagues at the University of California, San Francisco, show that treating MS with combinations of immune modulating drugs can greatly reduce MS disease. The researchers treated the "EAE mouse" model of MS with GA in combination with atorvastatin (Lipitor), a cholesterol-lowering drug shown to improve MS symptoms in clinical trials. Compared to EAE animals treated with either drug alone (which had no effect on established MS), EAE mice receiving the combination therapy demonstrated a significant prevention and reversal of clinical MS severity, with less myelin loss, CNS inflammation, and MS disease incidence. The authors then treated isolated inflammatory cells called macrophages with these drugs and found that the combination therapy mediated its effects by promoting the secretion of the anti-inflammatory molecule IL-10 and suppressed production of the proinflammatory molecules IL-12 and TNF-alpha. Importantly, the combined drug therapy utilized doses of each drug that were lower than the doses used in the single drug treatment method. These data suggest that combined delivery of drugs which act through different mechanisms may enhance the therapeutic efficacy of MS and reduce the negative side effects that result from treatment strategies which use the single drug delivery approach.
TITLE: Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity
Scott S. Zamvil
University of California, San Francisco, California, USA
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