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CONy 2022 | MIROCALS: low-dosage IL-2 for the treatment of ALS

Nigel Leigh, PhD, MBBS, PhD, FRCP, FAAN, FMedSci, University of Sussex, Brighton, UK discusses a Phase II randomized, placebo-controlled trial of low-dosage interleukin-2 (IL-2) as a therapeutic agent for amyotrophic lateral sclerosis (ALS). Modifying Immune Responses and OutComes in ALS (MIROCALS; NCT03039673) aimed to investigate if modifying immune responses through enhancement of regulatory T-cells (Tregs) modifies ALS disease progression rates. Early research noted that higher levels of Tregs in patients with early-stage disease were associated with improved survival. It is hoped that low dose IL-2 will boost Treg numbers and through crosstalk with the central nervous system, push microglial cells towards a cytoprotective phenotype. The trial is complete and data analysis is ongoing. This interview was conducted during the 2022 World Congress on Controversies in Neurology (CONy) meeting.

Transcript (edited for clarity)

It’s MIROCALS, it stands for Modifying Immune Responses and Outcomes in ALS. And the notion goes back to work really originating from Dr. Stanley Appel in Houston, where he observed that there was a relationship between the number of regulatory T-cells, Tregs, and survival, such that if you had more circulating Tregs in ALS, early on, you tended to survive longer. And that was quite a big effect in terms of relative risk and that went back to his interest in immune responses in ALS...

It’s MIROCALS, it stands for Modifying Immune Responses and Outcomes in ALS. And the notion goes back to work really originating from Dr. Stanley Appel in Houston, where he observed that there was a relationship between the number of regulatory T-cells, Tregs, and survival, such that if you had more circulating Tregs in ALS, early on, you tended to survive longer. And that was quite a big effect in terms of relative risk and that went back to his interest in immune responses in ALS.

There were other papers that supported that notion broadly. And so we all knew that Tregs are very dependent upon interleukin-2. Interleukin-2 has been used in cancer at high dosage when it’s very toxic, but at low dosage, it boosts the number of circulating regulatory T-cells, Tregs. And the notion then is that this will, through crosstalk with the central nervous system, may have an impact on microglial cells and pushing them if you like, towards a more cytoprotective phenotype than a cytopathic one.

And again, a lot of background evidence to support that, but no direct evidence of the efficacy of low-dose interleukin-2 in ALS. And that’s what we set out to do. So it’s this double-blind randomized control trial of low dose Interleukin-2 in patients with ALS. I’d love to tell you the result, but I can’t because we don’t have it. COVID has slowed us up. We are nearly there, but obviously, we will publish that in the appropriate ways.

So at the moment the trial is finished in terms of patient participation. We are cleaning and checking the data prior to database lock.

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