Anticholesterol Drug Found to Help Paralytic Mice

By DENISE GRADY

xperiments in mice suggest that statins, drugs normally used to lower cholesterol, may also prevent or lessen paralysis in people with some forms of multiple sclerosis, researchers are reporting today.

But the researchers warned that people with multiple sclerosis should not start taking statins in hopes of fighting the disease. The drugs must still be tested in people for that use. They may or may not work, and could even make the disease worse.

"We really urge that patients do wait for the results of clinical trials," said Dr. Scott S. Zamvil, an assistant professor of neurology at the University of California in San Francisco, and the senior author of a report on the research being published today in the journal Nature. Co-authors included researchers from Stanford, led by Dr. Sawsan Youssef and Dr. Lawrence Steinman.

Dr. Zamvil said the research team hoped to begin tests next year in people with very early signs of the disease; the patients will be given Lipitor, the statin used in the mice.

The National Multiple Sclerosis Society also said patients should wait. Dr. Stephen Reingold, the society's vice president for research programs, praised Dr. Zamvil's study, but, he added, "As attractive as it may be, there is no data to support the use of statins in multiple sclerosis" in people.

Dr. Reingold and other researchers said that some patients with multiple sclerosis were already taking statins because they also had high cholesterol. But no one knows whether the statins are affecting their multiple sclerosis.

Dr. Reingold said that normally, a mouse study would not receive a great deal of attention because such studies are considered an early phase of research. But in this case, he said, interest is high for several reasons. Statins are already on the market, and if they work, patients will welcome them, because existing treatments for multiple sclerosis are only moderately effective and must be injected several times a week, whereas statins come in pill form.

Although statins were approved by the Food and Drug Administration only for lowering cholesterol, doctors could legally prescribe them now for patients with multiple sclerosis. Once a drug is approved for one use, doctors can prescribe it for others.

The drug's manufacturer, however, is not allowed to label or promote the drug for a new use unless it goes through a new approval process.

A spokeswoman for Pfizer, which makes Lipitor, said she could not say "definitively" whether the company would seek approval for a new use of Lipitor if clinical trials showed it worked for multiple sclerosis. Lipitor is already the No. 1 selling drug in the world, with sales of $7 billion in 2001, according to IMS Health, which tracks the drug industry.

Pfizer did not pay for Dr. Zamvil's study, but did give him a $100,000 grant after the study was finished. His study was paid for by the National Institutes of Health, the National Multiple Sclerosis Society and private foundations.

About 300,000 Americans have multiple sclerosis. It affects nerves in the spinal cord and brain, and can cause weakness, paralysis, fatigue, cognitive problems and vision loss. Symptoms may come and go, and vary from mild to severe. The disease is not fatal.

Multiple sclerosis is an autoimmune disorder, in which the body fights its own tissues as if they were foreign. In this case, the target tissue is myelin, a fatty substance that coats nerve fibers. Cells in the immune system attack myelin, causing inflammation.

Researchers thought statins might help because studies had shown that the drugs, in addition to lowering cholesterol, could reduce inflammation. To test that theory, they used strains of mice in which they induced a disease much like multiple sclerosis. The mouse disease is considered a good model of multiple sclerosis, but not perfect: some drugs that have worked in the mice have also worked in people, but others have not, and some proved harmful.

The researchers gave Lipitor to small groups of mice, from 7 to 14 animals, with different forms of the disease, to see if the drug could prevent or treat relapses.

"The majority of the mice had markedly lessened paralysis," Dr. Zamvil said.

"These drugs have to be given under very careful medical supervision," Dr. Steinman said. Side effects can include liver abnormalities and muscle damage.