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Old Drug, New Use: New Research Shows Common Cholesterol-Lowering Drug Reduces Multiple Sclerosis Symptoms in Mice


For release: Monday, January 6, 2003

A new study shows that a widely prescribed cholesterol-lowering drug dramatically reduces symptoms of multiple sclerosis (MS) in mice. Results of the study suggest that statins, which are commonly used to prevent heart attack and stroke, could be a possible new treatment for MS and other autoimmune disorders. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) and appears in the November 7, 2002, issue of Nature 1 .

"These are very provocative results, because we've shown that statins can regulate the immune system response in an animal model for multiple sclerosis," says Scott Zamvil, M.D., Ph.D., assistant professor of neurology at the University of California at San Francisco and senior author of the study.

In the study, a daily dose of atorvastatin (brand name Lipitor), given for several weeks, reduced inflammation in the central nervous system and reversed some emerging paralysis in mice with a disease closely resembling MS, a disabling immune disorder affecting about 2.5 million people worldwide.

If the drug proves effective in human trials, statins, which can be taken in pill form, would offer an attractive alternative or complement to existing therapies for MS. Currently approved treatments are given by injection, often have serious side effects, and are only partly effective, Dr. Zamvil says.

"We don't know if or how well statins would work in reducing symptoms of MS in humans, but we do know that they are well tolerated when given orally," says Dr. Zamvil. Still, there are some risks. Statins can cause liver damage in a small percent of patients, and they carry a small risk of serious muscle damage.

Scientists believe MS develops when the body's immune cells led by so-called helper T cells attack myelin, the fatty insulating sheath surrounding nerve cells. The damage to myelin and the underlying neurons in both the brain and spinal cord leads to impaired cell communication and progressive physical disability.

MS symptoms include fatigue, vision problems, numbness, impaired balance, and paralysis. There are currently no treatments that can stop the disease, although a few treatments do slow its progression.

Atorvastatin appears to help the body produce protective molecules that fight inflammation and inhibit the production of toxic molecules, the researchers say. Previous studies in test tubes have also shown neuroprotective effects, suggesting that the drug might be used to treat such neurodegenerative diseases as Alzheimer's. "In the very near future we may have a variety of new uses for statins," Dr. Zamvil says.

Because statins have a different mechanism of action than current treatments, they may be able to work in tandem with other MS treatments. Since MS is a multi-stage disease, statins might be used along with approved treatments -- copaxone or beta interferons -- to treat the early, inflammatory stage of the disease and possibly to delay later stages, Dr. Zamvil says. Another drug, novantrone, is approved to treat symptoms related to later-stage neuron loss, he says.

The mouse findings support the results of a test-tube study of human blood samples published in the October 8, 2002, issue of Neurology 2 , which compared the effectiveness of three statin drugs to interferon beta proteins at reducing inflammation in human tissue samples. Dr. Zamvil says that because the two studies use different methods they are difficult to compare, but they both clearly show an anti-inflammatory effect of statins.

"Our study is a new stimulus for examining how statins might help patients in the early stages of MS and many other autoimmune diseases," says Dr. Zamvil. "But we'll have to wait for clinical trial results to see whether we can apply what we've learned to patients."

The researchers say their next step is to test the effectiveness of atorvastatin in patients with early stage MS.


1 Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS. "The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease." Nature, November 7, 2002; vol. 420, pp. 78-84.

2 Neuhaus O, Strasser-Fuchs S, Fazekas F, Kieseier BC, Niederweiser G, Hartung HP, Archelos JJ. "Statins as immunomodulators: Comparison with interferon-Beta1b in MS." Neurology, October 8, 2002; vol. 59, pp. 990-997.

- By Tania Zeigler



 

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Last Modified May 21, 2014