title: Role of statins in the treatment of multiple sclerosis.
abstract: Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely prescribed for hypercholesterolemia treatment. In the last years, statins have also been shown to exert immunomodulatory and anti-inflammatory effects which appear to be related to inhibition of isoprenylation of small GTP-binding proteins and, at least in part, independent of their cholesterol-lowering effects. These "pleiotropic" effects make statins an attractive treatment option for immune-mediated disorders such as multiple sclerosis. Studies in vitro and in experimental autoimmune encephalomyelitis animal model seem to support not only the efficacy of statins as immunomodulatory agents but also their potential neuroprotective properties, although the exact mechanism with which statins exert these effects has not yet been fully understood. The immunomodulatory, anti-inflammatory and neuroprotective properties of statins provided the incentive for several clinical trials in multiple sclerosis, in which they were tested not only as mono-therapy but also in combination with interferon-β. However, the attempt to translate the results of animal model studies in humans produced conflicting results. Further large, prospective, randomized, double-blind, placebo-controlled trials, designed to evaluate the long-term effects of statins alone or in add-on to other disease-modifying therapies, are needed to support their routine clinical use in multiple sclerosis.
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy. Electronic address: rciurleo@libero.it.
authors.forename: Rosella
authors.initials: R
authors.lastname: Ciurleo
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy; Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marino
mesh_terms: D000818:Animals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D018696:Neuroprotective Agents
keywords: Atorvastatin (PubChem CID: 60823); Combination therapy; Immunomodulatory effect; Lovastatin (PubChem CID: 53232); Multiple sclerosis; Neuroprotection; Randomized clinical trial; Simvastatin (PubChem CID: 54454); Statins