October 8, 2002
Oral drugs used to lower cholesterol, called statins, were shown in test tubes to inhibit immune responses of cells taken from individuals with MS:
Oral drugs used to lower cholesterol, called statins, were shown in test tubes to inhibit immune responses of cells taken from individuals with MS. This study was previously reported by Dr. Oliver Neuhaus (Karl-Franzens-Universitat, Graz, Austria) and colleagues at the April 2002 meeting of the American Academy of Neurology, and has now been published in the October 8, 2002 issue of Neurology. Clinical trials will be needed to determine whether these drugs can safely treat the immune attack in people with MS.
Previous basic studies suggest that statins can alter immune responses in a way that may hold promise in treating multiple sclerosis, which involves immune-system attacks against brain and spinal cord tissue.
Dr. Sawsan Youssef (Stanford University, Stanford, CA) and colleagues reported at the April 2002 meeting of the American Academy of Neurology that treating mice with the MS-like disease EAE with oral Lipitor® (atorvastatin) at the onset of their disease could reverse its paralysis, and that treating mice after an acute attack could resolve the attack. Looking at their brains and spinal cords, the treated mice appeared to have less damage than would be expected.
Dr. Neuhaus’s team examined the influence of several forms of statins, including mevastatin, simvastatin (Zocor®) and lovastatin (Mevacor®) on white blood cells (immune cells) in test tubes, taken from 74 individuals with relapsing-remitting or secondary-progressive MS and 25 healthy controls. Some of the individuals with MS were undergoing treatment with one or another form of the MS medication interferon beta, and some were not receiving any medication. The white blood cells were treated and tested in several ways to determine whether there was a difference in the way they “responded” in the presence of statins alone, interferon beta alone, or statins in combination with interferon beta, compared to untreated cells.
This study showed that all statins tested could inhibit the immune cells’ responses, the immune messenger proteins they released, and specific markers of inflammation, all of which are hallmarks of the immune attack involved in multiple sclerosis. Simvastatin was the most potent, followed by lovastatin and mevastatin. Interferon beta showed similar effects, and in combination the two drugs were even more effective at inhibiting immune activity. However, some immune messenger proteins that have been linked to the immune attack in MS, such as gamma interferon and IL-12, were markedly increased by statins.
While hopeful, this study carried out in test tubes cannot determine whether statins will actually help people who have MS or whether it can be safely given at doses that might be beneficial. Also, caution must be taken in interpreting these results because of the apparent stimulation of gamma interferon and IL-12. It also is unclear to what extent the different statins are interchangeable in terms of their immune-modulating effects. The authors conclude that further study of statins, possibly as a complementary therapy to interferon beta, in MS may be appropriate, but that careful evaluation of the mechanism of action of statins is necessary.
Clinical trials will be necessary to determine whether statin drugs
may benefit individuals with MS. There is already one small-scale trial
of Zocor under way in 32 people who have relapsing-remitting MS. This trial
is taking place at the Medical University of South Carolina (Charleston),
in collaboration with investigators at Yale University (New Haven, CT)
and at the University of Colorado Health Sciences Center (Denver). Other
studies are under consideration at this time by investigators and pharmaceutical
companies that manufacture and market statins for treatment of high cholesterol.
© 2002 The National Multiple Sclerosis Society