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Evaluation of HMG-CoA Reductase Inhibitors for Multiple Sclerosis

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Abstract

The disease-modifying agents currently used in the treatment of multiple sclerosis (MS) are not completely effective and are associated with adverse effects and high costs. Thus, alternative treatment options are highly desirable. HMG-CoA reductase inhibitors (statins), widely prescribed as cholesterol-lowering agents, may be a future treatment option for MS — either in an add-on therapy regimen or alone — as they have been shown to exhibit potent immunomodulatory effects. Several recent reports have demonstrated that HMG-CoA reductase inhibitors prevent and reverse chronic and relapsing experimental autoimmune encephalomyelitis, an animal model of MS. Furthermore, in vitro experiments with human immune cells have shown an immunomodulatory mode of action of HMG-CoA reductase inhibitors that is comparable to that of interferon-β, an established treatment for MS. An open-label clinical trial assessing simvastatin treatment in patients with MS revealed a significant decrease in the number and volume of new lesions, as assessed using magnetic resonance imaging, and a favourable safety profile. A large multicentre, placebo-controlled phase II clinical trial assessing atorvastatin in patients with a clinically isolated syndrome (i.e. a single clinical event that is indicative of demyelination, and that predisposes to the development MS) has recently been initiated. However, prospective placebo-controlled trials of HMG-CoA reductase inhibitors in definite MS are difficult to perform because of ethical and financial issues. Furthermore, overly optimistic reports in the popular media, as well as the often uncontrolled access to HMG-CoA reductase inhibitors by patients with MS, complicate the evaluation of HMG-CoA reductase inhibitors as a realistic future treatment option for MS.

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Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Neurology, Heinrich Heine University, Mooren-strasse 5, D-40225, Düsseldorf, Germany

    Oliver Neuhaus, Olaf Stüve & Hans-Peter Hartung

  2. Department of Neurology, University of Texas Southwestern, Dallas, Texas, USA

    Olaf Stüve

  3. Department of Neurology, University of California, San Francisco, California, USA

    Scott S. Zamvil

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  1. Oliver Neuhaus
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  2. Olaf Stüve
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  4. Hans-Peter Hartung
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Correspondence to Oliver Neuhaus.

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Neuhaus, O., Stüve, O., Zamvil, S.S. et al. Evaluation of HMG-CoA Reductase Inhibitors for Multiple Sclerosis. CNS Drugs 19, 833–841 (2005). https://doi.org/10.2165/00023210-200519100-00003

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