New combination treatment could extend the lifetime of people with amyotrophic lateral sclerosis (ALS)

ALS (also known as Motor Neuron Disease (MND)) affects around 45,000 people in Europe at any one time. It attacks the nerves that control movement (motor nerves) so muscles no longer work. It usually progresses relentlessly but at different rates in different people, with a quarter of people with ALS dying within a year of developing symptoms and more than half within two to three years of diagnosis. However, some people with ALS live for 10 years or longer.

The MIROCALS randomised clinical trial involved research institutions, medical centres and logistical organisations, across the UK, France, Italy, Sweden and Ireland. Queen Mary University of London, led by Professor Andrea Malaspina, has been a major contributor to this study. Researchers recruited 220 people newly diagnosed with ALS, who were initially treated with the drug riluzole before being randomised to receive either IL2LD or a placebo for 18 months. 

Interleukin-2 is a molecule known to regulate the immune system in humans. Low doses of interleukin-2 (IL2LD) have been found to specifically reduce inflammation by increasing the number of white blood cells known as regulatory T cells (Tregs) in the blood. The study was designed to discover whether adding IL2LD to riluzole treatment was safe, and whether reducing neuroinflammation helped slow the progression of ALS and increase the lifespan of patients post-diagnosis.

The trial demonstrated that IL2LD is safe, and detailed analysis of the results revealed a statistically significant survival benefit in about 80% of the study participants who had lower levels of a cerebrospinal fluid (CSF) biomarker (phosphorylated neurofilament heavy chain protein – pNFH) indicating the rate of motor neuron damage.  In these people, the risk of death at the end of the study was reduced by over 40%.

These findings provide encouraging evidence that modifying the immune system could be a useful strategy for altering ALS progression. While IL2LD is not currently licensed for ALS treatment, the MIROCALS results suggest that IL2LD should now be considered for development as a safe and well tolerated treatment for ALS, adding to the disease-modifying effect of riluzole.

Professor Malaspina, Honorary Professor of Neurology in the Blizard Institute's Centre for Neuroscience, Surgery and Trauma, and principal investigator in the MIROCALS study, said: "The publication of the results of the MIROCALS study is a milestone in the progress towards the development of novel treatments and in the understanding of the role of disease biomarkers in ALS clinical trials. It proposes the use of immunomodulation as a therapeutic strategy, broadening the spectrum of treatment options in rapidly progressive neurological disorders like ALS."

The results of the clinical trial have been published in The Lancet today.