A previously demonstrated effect of simvastatin in delaying progression in an advanced form of multiple sclerosis (MS) is not related to its effect on serum cholesterol levels, a study published in PNAS (28 May 2019) has suggested
The research took data from a trial where 140 people with secondary progressive MS were randomly assigned to either simvastatin or placebo for two years.
Using computational methods, the researchers programmed two scenarios — one where the effects of simvastatin on expanded disability status score and brain atrophy were directly related to total serum cholesterol and one where they were not.
They found that the second model was most likely, indicating the effects of simvastatin in MS were likely due to intermediates in the cholesterol synthesis pathway and not circulating cholesterol levels. However, the mechanism is still unknown.
“Although this study cannot provide a final answer as to what exactly is the reason for the success of statins in progressive MS, it directs future researchers toward certain pathways,” said lead author Arman Eshaghi, a researcher at UCL Queen Square Institute of Neurology.
 Eshaghi A, Kievit R, Prados F et al. Applying causal models to explore the mechanism of action of simvastatin in progressive multiple sclerosis. PNAS 2019;116(22):11020–11027. doi: 10.1073/pnas.1818978116