A new molecular treatment for Motor Neurone Disease (MND) has shown promising results in clinical trials, with an increase in survival at 21 months of 40% among participants with lower disease intensity.
The results of the MIROCALS (Modifying Immune Responses and Outcomes in ALS) Trial were presented at the 33rd International Symposium on ALS/MND last week by Dr Gilbert Bensimon, study coordinator, University Hospital of Nimes and the Paris-Sorbonne University, France, and Professor Nigel Leigh, study co-coordinator and chief investigator, BSMS.
The MIROCALS study was funded by The European Commission H2020 programme, the Motor Neurone Disease Association (MNDA) and the French Health Ministry with significant contributions from The MyName’5Doddie Foundation and ALS-related medical charities in France.
Nigel Leigh, Professor of Neurology at BSMS, said: “The study shows that low dose IL-2 improves survival and function in MND. This supports the core hypothesis that neuroinflammation is a target for MND therapy.
“The real heroes of this story are, of course, all the altruistic people with MND who volunteered to take part knowing they might be allocated to placebo, and that they were committing to three lumbar punctures, many blood tests and frequent visits to hospital. In the end, we hope that low dose IL2 may become a new treatment for ALS.
“Much more remains to be done to clarify the mechanisms by which inflammation and nerve cell damage interact, and that work is ongoing thanks to our funders, colleagues, collaborators, the biobank, and the inspiration of extraordinary people like the late Doddie Weir.”
MND is a progressive, disabling and often rapidly fatal disorder characterised by damage and death of motor nerve cells (neurons) in the brain and spinal cord resulting in weakness, muscle wasting, difficulty swallowing and breathing. Only one drug, riluzole, has been shown to slow the rate of progression of ALS, only slightly, and this was licenced in 1996.
From 2017 the study recruited 220 volunteers with MND to take part in a randomised double-blind trial comparing a low dose of the molecule interleukin-2 (IL2) against a dummy (placebo) injection. People with ALS were recruited into MIROCALS in 17 ALS Centres- 7 in UK and 10 in France.
The key measure of the effect of IL2 was survival at 21 months after starting treatment with IL2 or placebo. Day to day function was assessed by a standard scale known as the ALS Functional Rating Scale-Revised (ALSFRS-R), and by various other measures of disease progression. Quality of life was also assessed.
The results show that low dose IL2 treatment improved the chances of participants surviving at 21 months. The result was particularly striking when survival was measured in relation to a biomarker known as phosphorylated Neurofilament Heavy Chain (pNFH) in spinal fluid. Levels of pNFH in spinal fluid correlate very strongly with survival and thus provide a means to classify people according to disease ‘intensity’.
In people with relatively low levels of spinal fluid pNFH at the start of the study who had been allocated to active IL2 the risk of dying by 21 months was decreased by just over 40% compared to using placebo- that is, almost halving the risk of death by 21 months. However, people with very high levels of spinal fluid pNFH deteriorated rapidly and no benefit was seen, perhaps because these people deteriorated and died too quickly for the IL2 to have an impact.
The MIROCALS Consortium has united leading scientists and clinicians from UK, France, Sweden, and Italy to focus on finding a new treatment for ALS. The next step will be to approach- via a Pharma company- the Regulatory Agencies in UK, France and North America for advice on the next steps in developing IL2 as a viable treatment for ALS. The Consortium is energetically pursuing these issues and in the meantime Consortium members will continue to analyse and exploit the unique resource of data, blood and spinal fluid samples donated by the participants in this study.
Find out more about MIROCALS here >