Evaluation of HMG-CoA reductase inhibitors for multiple sclerosis: opportunities and obstacles.
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-beta, 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.
Neuhaus
Oliver
O
Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. oliver.neuhaus@uni-duesseldorf.de
Stüve
Olaf
O
Zamvil
Scott S
SS
Hartung
Hans-Peter
HP
D000818:Animals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors