Spring 2005

Can Statins Ameliorate MS?

More than two years ago, researchers at UCSF Medical Center discovered that cholesterol-lowering statins have beneficial immunomodulatory effects in treating multiple sclerosis (MS) in an animal model. The research, conducted by neurologist Dr. Scott Zamvil, and published in the journal Nature, reflects a growing interest in the beneficial effects that statins may have on a variety of disorders like MS, Alzheimer's disease, diabetes and arthritis.

Zamvil and his co-principal investigator, Dr. Emmanuelle Waubant, a neurologist, are beginning an international, multi-center clinical trial to extend their previous research and find out whether statins can benefit people with MS. "This will be the first placebo-controlled trial of statins for treating MS," Zamvil says. Zamvil previously did the basic research on how statins affected an MS-like condition in mice.

A group led by Inderjit Singh at the Medical University of South Carolina in Charleston, and Tim Volmer at Yale University Medical School, recently did a small (28 patients) open-label clinical trial of the statin Zocor (simvastatin). Their results, published in the journal Lancet, demonstrated that the number and volume of new CNS lesions measured by MRI decreased in MS patients with this treatment. While promising, the Singh study is not definitive, says Zamvil, because of the way that patients were selected and because it was not placebo-controlled.

Statins lower cholesterol by interfering with cholesterol-producing enzymes, but also inhibit the secretion of inflammatory cytokines. This has made statin drugs potential therapeutics for a host of disorders, such as Alzheimer's disease, osteoporosis and MS. If effective against MS, statins will likely become a very attractive therapy because there are so few approved drugs for MS and because statins are already widely available, Zamvil says.

Zamvil and Waubant are recruiting patients for the placebo-controlled clinical trial. The research project will study 152 patients at 15 research centers in the United States and Canada. The two researchers designed the protocol for the study, which will be coordinated by the Immune Tolerance Network.

To be eligible for the study, patients must present with their first attack of MS and have two or more brain lesions visible on an MRI. Patients enrolled in the trial will be given the maximum FDA-approved dose of the statin Lipitor (atorvastatin) during a one-year treatment phase, and then will be followed for six or more months.

One reason for studying patients in the earliest stages of the disease is that this period is likely to show the greatest therapeutic response to statins. "MS has an early inflammatory phase and a later degenerative phase in which there is less inflammation," Zamvil says. Fixed neural deficits that accumulate later in the disease may also mask subtle improvements resulting from the use of statins.

Another reason for working with patients in the earliest stages is that these patients are most likely not yet on existing MS therapies, says Waubant.

Patient protection has been a concern in the construction of the trial, since the group that is randomly assigned the placebo may be deprived of a useful therapy. Therefore, Waubant says, any patients who exhibit either three new brain lesions on MRI scans or an exacerbation of their symptoms will be provided with free beta-interferon therapy for the rest of the trial.

UCSF researchers are interested in what they might learn about statins' effect on MS, but also are excited by what they might learn about the disease itself, Waubant says. "Not much is known about the earliest stages of MS and we are going to be able to collect an enormous amount of information that has not been collected before."


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. 2002 Nov 7;420(6911):78-84.

2. Timothy Vollmer, Lyndon Key, Valerie Durkalski, William Tyor, John Corboy, Silva Markovic-Plese, Jana Preiningerova, Marco Rizzo, Inderjit Singh. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet, Volume 363, Issue 9421, page 1607.

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