Results of a phase 2 study published in The Lancet suggest that simvastatin, a cheap cholesterol lowering drug, might be a potential treatment option for the secondary progressive, or chronic, stage of multiple sclerosis (MS), which is currently untreatable.

Findings from the MS-STAT trial showed that a high, daily dose of simvastatin was safe, well tolerated, and slowed brain atrophy (shrinkage) by 43% over two years compared with placebo. Longitudinal studies suggest that atrophy progression is linked with disability.

In its early stages, MS is characterised by intermittent neurological symptoms, called relapsing-remitting MS. Within 10 to 15 years, more than half of patients develop secondary progressive MS, a steady worsening of symptoms and increase in disability. To date, no licensed drugs have shown a convincing impact on this later stage of the disease.

Statins have been shown to have anti-inflammatory and neuroprotective effects on the nervous system. An initial clinical trial of simvastatin in people with early-stage MS showed reductions in brain lesions, suggesting an effect on the underlying disease process. But subsequent trials have had conflicting results.

To investigate the potential of simvastatin in the progressive stage of MS, the MS-STAT trial randomly assigned 140 people with secondary progressive MS (aged 18–65 years) to receive either 80 mg of simvastatin or placebo for 2 years.

“In the progressive stage of MS the brain shrinks by about 0.6% a year. Our main measure of success was to reduce the rate of brain atrophy”, explains study leader Dr Jeremy Chataway of University College London Hospitals / UCL in the UK.*

Analysis of pre-treatment and post-treatment brain MRI scans showed a reduction in the average atrophy rate to 0.3% a year with simvastatin, a 43% reduction (when adjusted for factors such as age and gender) compared with placebo. Additionally, small but significant improvements were noted in both a doctor (EDSS) and patient-reported (MSIS-29) disability scale. Simvastatin was generally well tolerated and serious adverse events were similar between the two groups (20% placebo vs 13% simvastatin).

According to Chataway, “Caution should be taken regarding over-interpretation of our brain imaging findings, because these might not necessarily translate into clinical benefit. However, our promising results warrant further investigation in larger phase 3 disability-driven trials.”* This clinical trial is the culmination of long-standing research led by Professor John Greenwood at the UCL Institute of Ophthalmology showing the potential therapeutic benefits of using statins to treat autoimmune diseases such as multiple sclerosis and uveitis. According to Professor Greenwood, “After nearly two decades of research, it is immensely gratifying to see this work progress into the clinic to deliver benefits to patients.”*

Writing in a linked Comment, Jacqueline Palace from the John Radcliffe Hospital, Oxford, UK and Neil Robertson from Cardiff University in Wales say, “Chataway and colleagues’ study is a promising and novel development. The study is investigator led and has therefore focused on clinical need, targeting patients with progressive multiple sclerosis in whom most disability is incurred…The study also reports a predominant effect on neurodegenerative rather than inflammatory outcomes, suggesting a novel mechanism of action that might be suitable as combination treatment with immunomodulatory treatments…Further phase 3 studies to measure the effect of simvastatin on sustained disability, particularly in patients with non-relapsing secondary progressive and primary progressive multiple sclerosis, are clearly needed, but this trial represents a promising point from which to develop trials of progressive disease.”