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By Daniel DeNoon
WebMD Medical News
Reviewed By Louise Chang, MD
on Thursday, March 16, 2006
The second drug is Lipitor , one of the group of so-called statin drugs. Lipitor and its sister drugs lower cholesterol levels. However, the anti-MS activity of Lipitor appears to be separate from its cholesterol-lowering action.
A team led by University of California, San Francisco researcher Scott S. Zamvil, MD, PhD, in 2002 reported that Lipitor has anti-MS action in mice. An NIH-sponsored clinical trial is now enrolling people with first-episode MS to see if Lipitor can prevent more serious disease.
Now Zamvil's team reports that low doses of Lipitor and Copaxone -- doses too low to have any effect by themselves -- pack a powerful anti-MS punch. The combination prevents paralysis in mice with an induced MS-like disease.
Perhaps even more impressive, the combination treatment reverses paralysis in these mice.
"We have two drugs that are relatively safe in people. At the preclinical level we have shown they have a marked effect on MS," Zamvil tells WebMD. "We hope that by testing this in clinical trials there may be an added benefit of these two drugs when given in combination."
Don't Try Drug Combo Yet
Zamvil warns patients not to try this combination at home.
"Caution is advised. Remember these results, though provocative, are based on animal studies," he says. "Statins, even though widely used, can be associated with liver and muscle damage. The general doses for treating cholesterol are the lower doses -- and here we are testing the highest FDA-approved doses. So MS patients on Copaxone should not go out and grab their statins."
MS expert Jerry S. Wolinsky, MD, professor of neurology at the University of Texas-Houston Health Science Center, echoes Zamvil's warning.
Wolinsky notes that an earlier trial of combination therapy for MS -- Tysabri and beta interferon -- seems to have resulted in a rare but deadly side effect. The deaths led to the removal of Tysabri from the market (although an FDA advisory panel recommends bringing back the drug with strict limits on its use).
"You cannot say just because it works in the mouse, it works in people," Wolinsky tells WebMD. "A lot of folks out there are on Copaxone. And they know about the statins. And they ask me, 'Gee, doc -- should I be on a statin?' I say, 'Only if your cholesterol is up. And only at the dose needed to get your cholesterol down. But I am not going to put you on a statin -- particularly at the doses that might work on MS -- given the known side effects in people at these doses.'"
Paralysis Reversed in Mice
MS is a disease in which the body's immune system mistakenly attacks the myelin sheath coating nerve fibers. Myelin is important in the sending of nerve signals. There are several forms of MS:
- Relapsing-Remitting MS. About 85% of people with MS start with this condition. It's a vicious cycle of disease relapses and remissions. Disability gradually increases.
- Secondary-progressive MS. Untreated, about half of people with relapsing-remitting MS would go on to this condition, which is worsening of symptoms between relapses.
- Primary-progressive MS. Some 10% of people with MS have steadily accumulating disability from disease onset.
- Progressive-relapsing MS is a rare form of MS, with acute attacks and steadily increasing disability.
Treatments aim to disarm or deflect the improper immune responses that underlie MS. These treatments include beta interferon (Avonex, Betaseron, and Rebif), Copaxone, and the anticancer drug Novantrone. As noted above, Tysabri is currently unavailable but may soon return to the U.S. market.
Copaxone seems to pull the teeth from the immune cells that target MS. Lipitor and other statins, in an action separate from their anticholesterol effect, also affect the immune system.
Zamvil's team studied Copaxone and Lipitor in the mouse model of MS. These mice were given shots that gave them an MS-like disease.
The researchers found that low doses of Copaxone or Lipitor alone had no effect on disease in these mice. But a low-dose combination of the two drugs prevented MS. And in mice already paralyzed, the Lipitor/Copaxone combination reverses paralysis.
"Does this mean, wow, if we give these two drugs we will have a great effect?" Zamvil says. "We are hoping the two drugs together will have added benefit. But until we do the clinical trial in people, we won't know how much benefit and risk there will be."
"This combination is obviously a very good way to think about going," Wolinsky says. "But you really have to do the clinical studies."
SOURCES: Stüve, O. Journal of Clinical Investigation, March 16, 2006 online edition. Scott S. Zamvil, MD, PhD, associate professor of neurology and immunology, University of California, San Francisco. Jerry S. Wolinsky, MD, professor of neurology, University of Texas-Houston Health Science Center.
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