Cholesterol-lowering drug shows promise for MS treatment
Results of the first human clinical trial of simvastatin, a common cholesterol-lowering drug, for the treatment of relapsing-remitting multiple sclerosis (MS) showed promising indications of the drug’s effectiveness in the treatment of this variant of MS.The results of the study, directed by MUSC, were presented April 1 in Honolulu at the annual meeting of the American Academy of Neurology.
The
groundbreaking results of the first human clinical trial of simvastatin
for the treatment of multiple sclerosis were announced this week in Honolulu.
The clinical trial, which was directed by MUSC researchers, had its genesis
in the basic science laboratory of MUSC's Dr. Inderjit Singh. Singh
is pictured, center, with colleagues, Drs. Mushfiquddin Khan, Manjeet Krau,
Ajaib Singh and Ehtishamul Haq Shah.
The work had its genesis in an MUSC pediatric research laboratory six years ago when MUSC basic science investigators led by Inderjit Singh, Ph.D., found that a class of drugs known as “statins” were effective in reducing brain damaging inflammation in cell culture and in experimental animals. The results in the laboratory were dramatic, leading researchers to develop a human protocol to investigate the benefits of simvastatin as a treatment for MS.
“It is the most gratifying experience for me, as a basic science researcher, to see five years of tedious animal and cell research evolve into a potential treatment for a disease afflicting more than 2.5 million people worldwide,” Singh said.
“The primary marker we measured was the change in the number of active brain lesions associated with multiple sclerosis using MRI scans of the trial participants at intervals during the trial,” said Lyndon Key, M.D., chairman of the Pediatrics Department at MUSC, who designed the clinical trial with Singh and Timothy Vollmer, M.D., of the Barrow Neurological Institute in Phoenix.
Of the 28 participants who completed the trial, three showed no change in mean number of lesions between pre- and post-treatment brain MRIs; two showed an increase in lesions, and 23 showed a decrease in lesions. “Not only were the results positive, but we used a drug that is used safely by millions of people,” Key said. “The drug can be taken orally, rather than by injection like the drugs currently used for MS, and costs about a fifth that of other MS medications.”
The multi-center clinical trial to determine the efficacy of treatment with 80 mg per day of simvastatin began in December 2000 with three centers participating under the coordination of the Clinical Innovation Group, a full-service contract research organization (CRO), part of the MUSC Foundation for Research Development. The centers were MUSC with William Tyor, M.D., director of the MUSC Multiple Sclerosis Clinic, serving as the clinical principal investigator; Yale University with Timothy Vollmer, M.D., (currently at the Barrow Neurological Institute in Phoenix) as the clinical principal investigator and lead clinic clinician for the study; and the University of Colorado’s Denver Health Sciences Center with John Corboy, M.D., as clinical principal investigator.
With the help of the Clinical Innovation Group, Singh and Key received an unrestricted educational grant from Merck and Co., Inc. to conduct the study. Under the direction of Valerie Durkalski, Ph.D., the Clinical Innovation Group collected and housed the data from all three centers and provided the statistical support for the study design and data analysis.
“We
are proud of the role of MUSC’s Clinical Innovation Group in this groundbreaking
national study,” said Durkalski.
“The findings are still preliminary,” Tyor said. “Although they do show significant benefits are derived from simvastatin, it would be premature to suggest that everyone with MS should begin taking this drug.” This trial was done with a limited number of participants, and all the participants in the trial were given the active drug. The next step in the research requires a trial with a much larger number of participants with some on the drug and some not.
Another future research possibility is looking at a combination of simvastatin along with another MS drug. Future trials could assess the safety of the drug combination and the possibility of an enhanced effect.
“The evolution of this clinical trial is extremely interesting from
a scientific standpoint,” said Key. “Dr. Singh is a pediatric researcher,
who was interested in finding a treatment for adrenoleukodystrophy, a rare
genetic disorder in male children. In the course of his animal and cell
culture research, he found that statin drugs were effective in blocking
the activation of inflammatory cells. This had dramatic implications; not
just in the disease he was initially studying, but in a host of other illnesses
caused by inflammation, including MS, stroke, Alzheimer’s disease and spinal
cord injury. We are extremely pleased that the results of this clinical
trial demonstrate the drug’s potential as a treatment for MS. Also exciting
is the possibility of future scientific breakthroughs in the treatment
of other diseases caused by inflammation that could vastly improve the
health and wellbeing of future generations. We are proud that this very
important initial scientific breakthrough came from a Medical University
of South Carolina pediatric research team.”
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