Armed with promising evidence of the potential of certain anti-cholesterol medications known as statins in the treatment of multiple sclerosis (MS), medical experts are launching a large clinical trial to further test the safety and efficacy of these drugs.
Investigators at more than a dozen medical institutions are currently enrolling patients for this Phase 2 trial, which is planned to include 152 people at high risk for developing the illness. The drug being tested is atorvastatin (uh-TOR-vuh-stat-ihn), marketed as Lipitor by Pfizer.
Promising Evidence Uncovered
The trial is based on previous studies, both in animals and people, that have suggested that statins can alter immune responses and possibly reduce inflammation. It's believed the cause of MS lies in an abnormal immune response that attacks the body's own tissue as if it were foreign.1
In one of the most recent investigations to test the effectiveness of a statin in people with multiple sclerosis,2 doctors led by neurologist Timothy Vollmer, MD, of the Barrow Neurological Institute in Phoenix enrolled 28 patients to test simvastatin (Zocor/Merck).
Each patient in the open label pilot study was given oral 80 mg doses of simvastatin. Then, Vollmer's team conducted brain scans to determine whether the medication had been effective or not. "The mean number of lesions at months 4, 5 and 6 of treatment was compared with the mean number of lesions noted on pretreatment MRI scans," the researchers wrote.
At the end of the study, the number of brain lesions plunged 44%. The volume of each lesion also diminished by about 41%, Vollmer and his colleagues found. "Oral simvastatin might inhibit inflammatory components of multiple sclerosis that lead to neurological disability," the researchers concluded. Muscle weakness was the only side effect reported.
Animals Were Tested First
Similar positive findings have been shown in animals. Led by neurologist Scott Zamvil, MD, PhD, at the University of California at San Francisco and Sawsan Youssef, PhD, a postdoctoral fellow at Stanford University, the study used mice to test Lipitor against a disease induced in the rodents that is similar to MS known as experimental autoimmune encephalomyelitis (EAE).3
The researchers found that the drug prevented or reversed chronic or relapsing paralysis due to the disease in the rodents. "We showed immune modulation for the first time," said Zamvil, in an interview with Priority Healthcare.
Among other things, the drug promoted the production of certain anti-inflammatory molecules in the immune systems of the mice that protected them from contracting EAE. In fact, while the drug blocked production of proinflammatory molecules, it boosted production of these anti-inflammatory molecules at the same time. "That was one of the novel observations in the paper," explained Zamvil, who is an associate professor of Neurology at UCSF.
"There have been several different reports since that time that have confirmed our findings," he said.
In a later study, it was suggested that atorvastatin also helped block the movement of certain damaging immune system cells into the mice's central nervous systems where they would have attacked myelin.4
Latest Research Plans
In the new trial, which will be led by Zamvil and fellow UCSF neurologist Emmanuelle Waubant, MD, PhD, and will involve 14 centers in the US and Canada, patients will be selected at random to receive either 80 mg doses of Lipitor or an inactive placebo for a total of one year. At the end of the treatment period, each patient will be followed-up for a total of six months.
The trial will be recruiting people for the next 18 months, so initial results aren't expected for at least a couple of years, Zamvil stressed. "These are very difficult patients to recruit because you have to catch them early."
This won't include patients with established MS, he said, but people who've experienced their very first symptom—an attack of optic neuritis in one eye or an episode of numbness on one side, for example—lasting at least 48 hours that hints that they may be at risk for developing full-blown MS. The trial protocol also requires that patients be enrolled within 48 days of the onset of their symptoms.
Those who experience a clinical attack of MS during the study will have the option of receiving interferon treatment for the remainder of the trial. The researchers say each patient who has such an attack will also undergo neurological and MRI analysis as soon as possible.
One of the reasons statins are so appealing for people with MS is not only the possibility that they are effective, but also because of the way they're taken. "The incentive for these drugs is that they're given orally. We have no [oral] drugs at this time that are approved for MS," said Zamvil. "That's a key feature."
There also appears to be a lower risk of toxicity with statins, he said.
For more information on enrolling in the trial, visit ClinicalTrials.gov.
1. National Multiple Sclerosis Society. What Causes MS? Available at: http://www.nationalmssociety.org/What%20causes%20MS.asp. Accessed April 4, 2005.
2. Vollmer T, Key L, Durkalski V et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004 May 15;363(9421):1607-8.
3. Youssef S, Stuve O, Patarroyo JC et al. The HMG-CoA reductase inhbitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002 Nov 7;420(6911):78-84.
4. Aktas O, Waiczies S, Smorodchenko A et al. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J Exp Med 2003 Mar 17;197(6):725-33. Epub 2003 Mar 10.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
