Larger Studies Needed
May 14, 2004
The National Multiple Sclerosis Society
An article was published in the May 15, 2004 issue of the journal The Lancet describing a small clinical trial of the oral cholesterol-lowering drug Zocor® in 28 individuals with relapsing-remitting MS:
Results of a small pilot study, previously reported in April 2003 at the Annual Meeting of the American Academy of Neurology, have now been published in the May 15, 2004 issue of the journal The Lancet (Vol. 363; 1607-1608). Drs. Timothy Vollmer (Barrow Neurological Institute, Phoenix), Inderjit Singh (Medical University of South Carolina) and others found that the cholesterol-lowering pill Zocor® (simvastatin, Merck & Co., Inc.) safely reduced the number of number and volume of “gadolinium-enhancing” MRI-detected brain lesions (generally interpreted to be new lesions) over the six-month treatment period in 28 people with relapsing-remitting MS. Larger, controlled studies will need to be conducted to ascertain the safety and effectiveness of Zocor or other statins for MS.
Such trials are in planning stages.
Previous studies have suggested that cholesterol-lowering “statins” can alter immune responses in a way that may hold promise in treating MS. For example, Dr. Oliver Neuhaus (Karl-Franzens-Universitat, Graz, Austria) and colleagues reported that in cells taken from individuals with MS, different forms of statins were capable of inhibiting several immune responses and markers of inflammation typically involved in MS (Neurology, October 8, 2002). However, in those studies, statins stimulated the release of some messenger proteins known to increase inflammation as well, making their ultimate value in treating MS uncertain. Additional studies on statins have been published, including one by Drs. Scott Zamvil (University of California, San Francisco) and Sawsan Youssef (Stanford University) and others, who reported (in November 7, 2002 Nature) that Lipitor (atorvastatin, Pfizer, Inc.) prevented or reversed the MS-like disease EAE in mice. The mechanism underlying the drug’s ability to treat EAE appears to be immune system modulation, rather than a cholesterol-lowering mechanism.
This Study: Individuals with relapsing-remitting MS at multiple medical centers, including Yale University, Medical College of South Carolina, and the University of Colorado at Denver participated in this first human study of a statin in MS. After undergoing monthly MRI (magnetic resonance imaging) scans for three months, those 30 individuals who had at least one new MRI lesion were then eligible for six months of treatment with 80 mg. of oral Zocor daily. During the study, participants underwent neurological assessments and MRI scans, and blood samples were also taken. The primary outcome that investigators looked at was the difference in the mean number of gadolinium-enhancing lesions between scans taken during pre-treatment, and during months 4, 5 and 6 of the treatment period. Secondary outcomes were drug safety, other MRI results, and changes in neurological assessments and immune system activity. This was an “open-label” study, meaning that all patients received Zocor, and the effects of this treatment were not compared with those of an inactive placebo.
The investigators report a significant (44%) decrease in the mean number of gadolinium-enhancing lesions, and a decreased volume of gadolinium-enhancing lesions, in the 28 individuals who completed the study. They found no differences in immune responses that would suggest a shift away from inflammation, and there were also no differences observed in neurological status or disability in this short study. No serious adverse events related to treatment occurred.
This small study, indicating possible benefit on MS lesion development, shows promising results for statins in treating people with relapsing-remitting MS. However, the safety and effectiveness of this treatment must be ascertained in larger, controlled trials. Such studies of statins are now in the planning stages.
Among some issues to be sorted out are, which of the available statins might be the best potential therapy for MS, and whether the high doses used in this study can be safely used over longer periods of time. Currently, there is no indication that the use of statins at the doses generally used for lowering cholesterol are of any value in the treatment of MS, and there are no data to suggest that individuals with MS who use statins to control cholesterol levels have had benefits in terms of their MS.
Individuals concerned about the role of statins in MS should discuss
the results of this study with their personal physicians.
Copyright © 2004, The National Multiple Sclerosis Society