Posted on 11/07/2002 2:04:34 PM PST by shrinkermd
Widely used cholesterol-lowering drugs could relieve multiple sclerosis, say researchers. The drugs might also work on other diseases where the immune system attacks the body.
The drugs, called statins, are commonly prescribed to fight heart disease. The new study shows that they may also work on the immune system, reducing brain inflammation.
Multiple sclerosis is thought to arise when the immune system assaults the nervous system. It strikes with unpredictable symptoms including fatigue, tremor and paralysis. Existing treatments can slow, but not stop, the advance of the disease.
Scott Zamvil of the University of California, San Francisco, and his team tested a drug called atorvastatin - which has the brand name Lipitor - on three different mouse versions of the disease.
The results were "overwhelming", says Zamvil. A week's treatment equivalent to the highest human dose reversed or prevented relapses and curbed brain inflammation. The group hopes to start clinical trials in humans early next year.
The drug has few side-effects and is taken by mouth. It is an attractive candidate for desperately needed therapies, says multiple-sclerosis researcher Hartmut Wekerle of the Max-Planck Institute of Neurobiology near Munich, Germany. Current drugs require repeated injections.
Statins were known to influence the immune system. They can prevent the rejection of transplanted organs, and previous studies hinted that they might combat multiple sclerosis. Now Zamvil's team has begun to work out how.
Atorvastatin seems to work on the T cells in the immune system that attack the brain in multiple sclerosis. The drug seems to convert them into cells that fight inflammation, the researchers found. "They turn from culprits to benefactors," says Wekerle.
The T cells churn out fewer molecules that cause inflammation, and more of those that relieve it. Transplanting statin-treated T cells into diseased mice eased the animals' symptoms.
Statins might influence T-cells by preventing their target brain cells from displaying the surface proteins that trigger attack, speculates Zamvil. Alternatively, the changes in the immune system might be a by-product of lowered cholesterol.
Multiple sclerosis affects up to 2.5 million people worldwide. But many more suffer from other autoimmune diseases, such as diabetes and rheumatoid arthritis, which hit the pancreas and joints, respectively. The prospect that statins might work on other diseases is exciting, says Zamvil - "but we need clinical trials".
References
Youssef, S. et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature, 420, 78 - 84, (2002). |Article|
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