Statins and their potential targets in multiple sclerosis therapy.
Multiple sclerosis (MS) is a CNS-demyelinating disease characterised by relapsing and chronic neurological impairment. While traditionally CNS autoantigen-specific CD4(+) T cells have been considered the culprits in the initial phase of the disease, recent observations have altered this concept. It is now recognised that other T lymphocyte subclasses can initiate CNS demyelination. In addition, other cell types and molecules may play an important role in MS pathogenesis. There is overwhelming evidence that MS is a dynamic process, in which recurrent episodes of blood-brain barrier disruption and CNS inflammation play a crucial role in early disease stages, leading eventually to the largely irreversible changes of demyelination, gliosis and axonal degeneration. These observations may have important therapeutic implications. Within the last ten years, several medications have been approved for MS treatment. These agents, all of which are given parenterally, are only partially effective and are often associated with adverse effects and potential toxicities. The number and different types of medications used for MS are likely to increase in the near future, as several novel therapies are currently tested in clinical trials. 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, 'statins', are cholesterol-lowering drugs that are given orally, are safe and have biological effects independent of their cholesterol-reducing properties. Recent reports have shown that statins have anti-inflammatory and neuroprotective properties that may be beneficial in the treatment of MS. This article will outline experimental evidence that suggests potential clinical benefits of statins for MS patients.
D000328:Adult; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007371:Interferon-gamma