November 6, 2002
Lipitor® (atorvastatin, Pfizer, Inc.), an oral drug used to lower cholesterol, was shown by investigators at University of California, San Francisco and Stanford University to prevent or reverse the multiple sclerosis-like disease EAE in mice:
Lipitor (atorvastatin, Pfizer, Inc.), an oral drug used to lower cholesterol, was shown to prevent or reverse the MS-like disease EAE in mice. The mechanism underlying the drug’s ability to treat EAE appears to be immune system modulation, not a cholesterol-lowering mechanism. This study, previously reported by Drs. Scott Zamvil (University of California, San Francisco) and Sawsan Youssef (Stanford University) and colleagues at the April 2002 meeting of the American Academy of Neurology, has now been published in the November 7, 2002 issue of Nature. This study was partly supported by two research grants and a postdoctoral fellowship grant from the National MS Society. Clinical trials in MS will be needed to determine whether Lipitor can safely treat the immune attack against brain and spinal cord tissues which underlies multiple sclerosis in people. Dr. Zamvil is planning a clinical trial in persons who are at high risk for developing MS.
Previous basic studies suggest that Lipitor and other “statins” can alter immune responses in a way that may hold promise in treating multiple sclerosis. Dr. Oliver Neuhaus (Karl-Franzens-Universitat, Graz, Austria) and colleagues recently reported (Neurology, October 8, 2002) that in cells taken from individuals with MS, several forms of statins were capable of inhibiting several different immune responses and markers of inflammation typically involved in MS. However, in those studies, statins stimulated the release of some messenger proteins known to increase inflammation as well. A new report related to statins now demonstrates a potential role for controlling immune responses and disease course in laboratory mice with EAE, an MS-like disease.
Dr. Zamvil and colleagues administered Lipitor daily – at doses equivalent to and higher than those used to lower cholesterol in humans – to mice with three forms of EAE: relapsing disease with periods of remission; chronic, long-standing disease; and severe disease. Lipitor was chosen because laboratory studies suggested it may be more potent than other statins in regulating the immune response. After 12 days, the mice were examined for evidence of disease improvement and for changes in immune response.
Lipitor effectively treated all three types of EAE. Relapses were prevented or remitted in the relapsing model, and brain tissue damage was greatly reduced. In chronic EAE, clinical symptoms improved significantly. Severe EAE was suppressed. The best results seemed to come from the highest doses of drug – a dose equivalent to about 10 times that used safely in humans for cholesterol control. Lipitor appears to affect the immune attack underlying EAE on several fronts: inhibiting genes that instruct proteins in the immune attack; reducing activation of immune cells that drive the attack; decreasing infiltration of immune cells and proteins into the brain; and inducing immune messenger proteins that suppress the immune attack while inhibiting proteins that contribute to inflammation.
While hopeful, this study carried out in mice with an MS-like disease cannot determine whether Lipitor or any other statin will help people who have MS or whether it can be safely given at doses that might be beneficial. Clinical trials will be necessary to determine whether statin drugs may benefit individuals with MS. Dr. Zamvil is planning a clinical trial in people who are at high risk for developing MS. One small-scale trial of a different cholesterol lowering statin Zocor® (simvastatin, Merck & Co., Inc.) is under way in 32 people who have relapsing-remitting MS at the Medical University of South Carolina (Charleston), Yale University (New Haven, CT), and the University of Colorado Health Sciences Center (Denver). Results are not yet available.
Individuals concerned about the possible benefits of statins for MS should discuss the results of this study with their personal physicians.
-- Research Programs Department
© 2002 The National Multiple Sclerosis Society