Statins, the widely used cholesterol-lowering drugs, could also treat the disabling disease multiple sclerosis (MS), according to research in the 7 November issue of Nature. Scott Zamvil and colleagues used mouse models of MS to show that oral atorvastatin prevented or reversed chronic and relapsing paralysis.

There are five statins available at present: lovastatin, simvastatin, pravastatin, fluvastatin and atorvastatin. They inhibit the enzyme HMG-CoA reductase, which controls the rate of cholesterol production in the body. These drugs lower cholesterol by slowing down its production, and by increasing the ability of the liver to remove the harmful low-density lipoprotein (LDL) cholesterol already in the blood. Statins have been used for more than 20 years now, and are a cheap and relatively safe treatment for atherosclerosis and coronary heart disease. Studies have also shown that statins can inhibit the production of pro-inflammatory molecules.

MS is thought to arise when autoimmune helper T cells attack the myelin sheath of the spinal cord and neurons, causing unpredictable symptoms, which range from fatigue and vision problems to paralysis. Current treatments include the use of interferon-β, which reduces the inflammation associated with nerve damage, or copaxone, a synthetic, basic, random co-polymer that is thought to inhibit the autoimmune attack. However, these treatments slow rather than stop the progression of the disease.

When tested in experimental autoimmune encephalomyelitis (EAE) mice, which are widely used as models for human MS, atorvastatin had a beneficial effect, preventing disease relapse and reducing inflammation in the nervous system. Atorvastatin seems to redirect myelin-specific helper T cells from a destructive autoimmune role to one of suppressing autoimmunity. A subset of helper T cells no longer produces inflammatory cytokines, but rather anti-inflammatory ones. Although cholesterol reduction could affect the behaviour of helper T cells, the authors have found another explanation for the effects described in their paper: atorvastatin inhibits the expression of a key immune-system protein, the class II transcriptional activator (CIITA), which controls the expression of major histocompatibility complex (MHC) class II molecules. Without the expression of MHC class II molecules on certain immune cells, helper T cells cannot be activated, and consequently, they are not destructive. It is not clear whether the reduction in CIITA expression is caused directly by atorvastatin, or is an indirect effect of reduced inflammation.

Statins are in clinical trials at present for human MS, and would make a cheap, orally available therapeutic for MS. However, results from EAE models are not always found to be reproducible in humans, and sometimes give the opposite outcome to that seen in man.