Alzheimer disease, antihypertensive therapy, diuretics, potassium-sparing diuretics
Atorvastatin (Lipitor) might prevent the progression and reverse the severity of multiple sclerosis (MS), according to investigators from the University of California, San Francisco (UCSF), and Stanford University Medical Center. The team examined the effects of treatment with a combination of glatiramer acetate (GA) and atorvastatin in murine models of autoimmune encephalitis (EAE). The investigators specifically examined whether atorvastatin could augment the efficacy of GA when GA and atorvastatin were given at suboptimal doses.Dramatic benefit from the statin/GA combination was seen. In the first part of the study, 10 mice received combination treatment before being given the protein that induces EAE. Paralysis, which was mild, developed in only 3 of these mice. The CNS tissue also showed fewer destructive inflammatory lesions. Evidence that the mice were producing fewer pro-inflammatory cytokines and more anti-inflammatory cytokines also was documented.In the second part of the study, combination therapy dramatically reduced clinical and histologic signs of MS in 10 mice with established EAE. The mice had no paralysis and reduced CNS inflammation and less destruction of the myelin sheath. The disease process was not reversed in mice receiving either no drug or monotherapy with suboptimal doses of either atorvastatin or GA.Coinvestigator Scott Zamvil, MD, PhD, associate professor of neurology at UCSF, noted that "agents with differing mechanisms of immune modulation can combine synergistically to treat CNS autoimmunity. We hope that the combination of atorvastatin and GA will prove beneficial in MS treatment."Treatment options for persons with MS have, to date, yielded disappointing results. They are only partially effective, can cause intolerable side effects or toxicity, and the long-term effectiveness of certain medications is questionable. Until better medications can be found, one strategy to improve outcome for patients would be to prescribe combinations of medications with additive or complementary effects."Statins and glatiramer work by entirely different mechanisms, yet have an additive effect. Each has low toxicity individually, and we expect their combined toxicities to remain modest," commented coinvestigator Lawrence Steinman, MD, professor of neurology and director of the Program in Immunology at Stanford University. He added that the cost of combination therapy involving a statin should please managed care organizations, because statins are relatively inexpensive.For more information about this study, see Stuve O, Youssef S, Weber MS, et al. Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J Clin Invest. 2006;116:1037-1044.