Cholesterol Drugs May Help MS Patients
A widely used family of cholesterol-lowering drugs called statins may provide an effective, inexpensive treatment for multiple sclerosis, several studies suggest.
One small trial in humans is already underway and a second, larger one will probably begin early next year, researchers said Wednesday.
The statins have revolutionized the treatment of heart disease, reducing heart attack deaths substantially in patients with high cholesterol levels and even in those with normal levels. The new studies suggest that the drugs will also prove valuable in treating autoimmune diseases -- not only multiple sclerosis, but perhaps insulin-dependent diabetes, rheumatoid arthritis and others.
Despite the successes in animals, experts cautioned physicians against prescribing the drugs for MS patients before trials are completed.
“We know these drugs are pretty safe when given to people who have high cholesterol, who are usually older and who have heart disease,” said Patricia A. O’Looney, director of Biomedical Research Programs for the National Multiple Sclerosis Society. “The question is, can it be given safely to someone who has MS, who is younger and who has regular cholesterol levels?”
Researchers are excited nonetheless because the preliminary results look promising. In addition to the two previously mentioned trials, researchers are also drawing up plans for other trials in which statins would be used in conjunction with existing therapies in an effort to boost their effectiveness. “There are going to be many other trials,” said Dr. Scott Zamvil of UC San Francisco, who led the trial.
Multiple sclerosis is an autoimmune disease that afflicts an estimated 250,000 to 350,000 people in the United States and more than 1 million worldwide. For reasons that are not clear, the immune system of patients attacks and destroys the myelin sheathes that, like the insulation on copper wire, coat nerve fibers.
Destruction of the myelin, in effect, short-circuits the nerves, leading to a spectrum of symptoms, including poor muscle control, paralysis, blindness, brain damage and death. Current treatments include three forms of synthetically produced interferons and a totally synthetic polymer called copaxone. Each of these must be given by injection, and they are expensive, ranging from $10,000 to as much as $17,000 per year. They are effective only about a third of the time, and they can have significant side effects.
Statins, in contrast, are taken orally and are substantially cheaper. They have been taken by millions of Americans and have few side effects, although liver and muscle damage can occur in rare cases. The drugs block the synthesis of cholesterol in the liver.
The current research on statins was stimulated by a 1995 UCLA study that showed that heart transplant patients who received the drugs were significantly less likely to reject the donor organs, independent of the drugs’ effects on the patients’ cholesterol. Statins are now used routinely in such patients to help reduce rejection.
A variety of animal and tissue culture experiments since have shown that the drugs reduce inflammation in humans. Last month, German and Austrian researchers reported that statins could alter the activity of cultured immune cells taken from patients with MS, changing the cells into a form that would no longer attack myelin.
A team headed by UC San Francisco’s Zamvil and immunologist Sawsan Youssef of Stanford University studied mice with an experimentally induced disease called EAE that closely resembles MS. They report in today’s issue of Nature that Lipitor -- also known by its generic name atorvastatin -- significantly delayed progression when given in the early stages of the disease. It also reversed paralysis when given in later stages.
“The animal data is quite striking,” Zamvil said. “We have to be cautious because it is an animal study, but it is really quite exciting.”
Zamvil is seeking approval from the Food and Drug Administration for a multi-center clinical trial that will enroll 126 patients who have had an initial episode of MS. The one-year study will examine whether an 80-milligram daily dose of Lipitor will prevent progression to full-blown MS. That is the highest dose approved by the FDA for lowering cholesterol. USC will be the L.A. center for the trial.
Another team already is conducting a trial in which 32 patients with relapsing-remitting MS are being treated with simvastatin, which is commonly known by the brand name Zocor.
