UCL Queen Square Institute of Neurology


European trial for amyotrophic lateral sclerosis reports positive top line results

7 December 2022

A large study which UCL and UCLH are part of suggests a type of immunotherapy can improve survival rates in amyotrophic lateral sclerosis (ALS). Results indicate that for patients with less aggressive disease progression, risk of death could be reduced by 40%

The MIROCALS study (Modifying Immune Response and Outcomes in ALS) is looking at use of low dose interleukin 2 (id IL2) in ALS – a condition that attacks the nerves that control movement so muscles no longer work. It kills a third of people within a year and currently there is no cure.

At UCL and UCLH, the study was conducted at the NIHR UCLH Clinical Research Facility (CRF) Leonard Wolfson Experimental Neurology Centre (LWENC), the National Hospital for Neurology and Neurosurgery and UCL Queen Square Institute of Neurology, with Dr Nik Sharma as local Principal Investigator.

Top line results from the study were presented today by Dr Gilbert Bensimon, from the Centre Hospitalier Universitaire de Nîmes, on the opening day of the Motor Neurone Disease Association’s 33rd International Symposium on ALS/MND. The trial, involving research groups in the UK, France, Italy and Sweden, tested whether low doses of IL2 can alter aspects of the immune system associated with inflammation in the central nervous system, which is believed to play an important role in the speed at which ALS progresses.

220 people with ALS recruited shortly after diagnosis were randomised in equal proportion to receive low dose IL2 or placebo for 18 months. The primary measurement was the mortality rate. The study found the treatment was well tolerated, with adverse events recorded as mostly mild to moderate, occurring across both active treatment and placebo arms. The study confirmed results of a previous pilot study which showed that IL2 decreases inflammatory markers in the blood.

Initial analysis of survival showed a small (19%) but not statistically significant decrease in the risk of death at 21 months. However, further analysis showed a larger and statistically significant treatment effect on survival. This effect was not present in participants who had aggressive, fast progressing disease – around 20% of patients. But for around 80% of participants with less aggressive disease progression, there was a significant decrease in the risk of death by over 40%.

The severity of disease progression was highly linked to levels of a substance found in cerebrospinal fluid called phosphorylated neurofilament heavy chain (CSF pNFH) – the primary biomarker used in the study.  The results provide encouraging evidence in support of altering ALS disease progression through immune system modification and approaches addressing neuroinflammation. 

andrea malaspina
  Prof Andrea Malaspina, of the UCL Queen Square Motor Neuron Disease Centre, Principal Investigator of the international MIROCALS consortium, commented: "This is a significant development in the right direction for individuals living with ALS. I thank all patients, Dr Nik Sharma and the NIHR UCLH CRF Team. Their work has been major contribution to the development of novel therapeutics for ALS."
 Professor Vincenzo Libri, Director of the NIHR UCLH CRF and LWENC said: “We are proud at the CRF to have been part of this research which represents a real step forward in the possible treatment of ALS, a neurodegenerative disease with such a huge unmet need. I want to thank all patients who were part of this research and our staff at the CRF who delivered it.”

Dr Bensimon, lead investigator and project co-ordinator, said: “MIROCALS is the first large scale randomised placebo-controlled trial to demonstrate ‘proof of principle’ in relation to IL2 with the potential to translate into clinical benefit for people living with this devastating condition.”
Professor Nigel Leigh, co-lead and chief trial investigator, of Brighton and Sussex Medical School, said: “There remain many questions to address, but the wealth of data and samples accumulated are supporting ongoing research to better understand the factors that drive ALS disease progression. These will hopefully open the door to new therapeutic avenues and more personalised approaches to treatment, to deliver even more positive outcomes in future trials.
Dr Brian Dickie, Director of Research for the UK-based Motor Neurone Disease Association, said: “ALS is a relentlessly progressive and devastating disease that robs people of their independence and ultimately their lives. Taking part in clinical trials requires a significant commitment from people with ALS and we are so grateful of everyone who volunteered for this important and ground-breaking study.”