Treatment with a molecule known as interleukin-2 (IL-2) may help reduce the inflammatory response in Motor Neuron Disease (MND), according to a new study by an international consortium, which included Brighton and Sussex Medical School (BSMS).
Although the cause of Motor Neuron Disease, also known as Amyotrophic lateral sclerosis (ALS), is not fully understood, it is known that inflammatory mechanisms influence motor neuron damage in the brain and spinal cord. Circulating regulatory T cell lymphocytes (Tregs) contribute to the control of this inflammatory response.
IL-2 is vital for the survival and function of Tregs, and used in low doses is well tolerated and increases Treg numbers and function in the blood.
The randomised controlled trial (IMODALS: Immune Modulation in ALS) found that treatment with ld IL-2 significantly increased the numbers of circulating Tregs and 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 ld IL-2 is fully functional in MND patients. Furthermore, this response was related to the dose of IL-2, which was found to be safe and well tolerated by the trial participants.
The study also found that changes in blood cytokines and chemokines were in keeping with the notion that ld IL-2 reduces the harmful effects and enhances the beneficial effects of immune activity in the nervous system in MND.
The double-blinded study involved 36 people with MND, randomly assigned to three groups of 12 participants. Each group received one of two subcutaneous doses of ld IL-2, or placebo over five days every month over three months. Observations on safety continued for a further three months.
Professor Nigel Leigh, Professor of Neurology at BSMS, who with Dr Gilbert Bensimon (University of Paris and Centre Universitaire Hospitalier de Nîmes, France) planned and co-led the study, said: “This randomised controlled trial of Interleukin 2 shows promising early results, and could eventually lead to new treatments for motor neuron disease. Our findings strongly support further investigation of ld IL-2 in MND and provide crucial insights on which to base larger trials designed to detect improvement in day to day activity and survival in the disease. Indeed, we are currently leading a much larger trial of ld IL-2 in AL, due to be completed in July 2021: (MIROCALS: www.mirocals.eu).”
The consortium of clinical and laboratory scientists from France, UK, Italy, and Sweden published the study with open access in the Journal EBioMedicine published by The Lancet, 7 July 2020 (DOI: 10.1016/j.ebiom.2020.102844).