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07 July 2020

Potential new treatment for ALS shows promise in clinical trial

Researchers have disclosed the results of a potential new treatment for amyotrophic lateral sclerosis (ALS).

als therapies promising

The study, conducted by a consortium of clinical and laboratory scientists from King’s, France, UK, Italy and Sweden, has been published today in the Lancet EBiomedicine.

Although ALS is a neurodegenerative disease, researchers are also interested in events happening outside the brain and spinal cord, in particular whether changes in the immune system might play a role in influencing the course of the disease. This is a subject which has been explored before, with particular reference to the ongoing MIROCALS drug trial of interleukin-2 (IL-2).

Although the cause of ALS is not fully understood, it is known that inflammatory mechanisms influence motor neuron damage in the brain and spinal cord. White blood cells, known as regulatory T cell lymphocytes (Tregs) are known to contribute to the control of this inflammatory response.

Tregs play a role in the immune system and are dependent on IL-2 for survival and function. At low doses, as used in IMODALS, IL-2 is well tolerated and has been shown to increase Treg numbers and function in the blood.

The IMODALS study had three main goals. The first goal was to show that low doses of IL-2 amplify Treg numbers and function in ALS patients and that any change seen was related to the dose of the drug.

Secondly, it was important to ensure that IL-2 at the chosen doses would be safe to use in people with ALS in longer term trials such as MIROCALS.

Thirdly, the study provided an opportunity to investigate in great detail the ways in which low doses of the drug modify some of the complex immune mechanisms, hopefully in ways that might be beneficial in ALS.

The third goal required regular blood sampling over the three-month period of the trial to measure the numbers, function, and types of Tregs and of other circulating immune cells, and to test the hypothesis that low dose IL-2 should alter the levels of specific chemical messengers known to be key players in the immune system, as well as looking at markers of nerve cell damage in ALS.

The double-blinded study involved 36 people with ALS, who were randomly assigned to three groups of 12 participants. Each group received either one of two doses of IL-2, or placebo, by an injection under the skin, over five days every month, for three months. As changes to the immune system can be long lasting, the clinical safety observations continued for a further three months.

The main findings were that low dose IL-2 significantly increased the numbers of circulating Tregs, as predicted, and - importantly - improved their ability to control other immune cell responses that contribute to nerve cell damage.

This double benefit of ‘more Tregs’ and ‘better Tregs’ indicates that low dose IL-2 therapy is fully functional in ALS patients. Furthermore, this response was related to the dose of IL-2, with higher levels of Tregs in the participants who received the higher dose.

Dr Tim Tree, from the School of Immunology & Microbial Sciences

Importantly, IL-2 was safe and well tolerated by the ALS trial participants.


Overall, these findings strongly support further investigation of IL-2 in ALS and have provided crucial insights for the ongoing MIROCALS trial which seeks to detect improvement in day to day activity and survival in ALS over a much longer 18-month trial period and is scheduled to finish towards the end of 2021.



In this story

Timothy  Tree

Professor of Immune Regulation and Immunotherapy