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The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low\u2010dose (ld) interleukin\u20102 (IL\u20102). We propose a pharmacometabolomics approach to decipher metabolic modifications occurring in patients treated with ld\u2010IL\u20102 and its relationship with Treg response. Blood metabolomic profiles were determined on days D1, D64, and D85 from patients receiving 2 MIU of IL\u20102 (\n                    <jats:italic>n<\/jats:italic>\n                    = 12) and patients receiving a placebo (\n                    <jats:italic>n<\/jats:italic>\n                    = 12). We discriminated the three time points for the treatment group (average error rate of 42%). Among the important metabolites, kynurenine increased between D1 and D64, followed by a reduction at D85. The percentage increase of Treg number from D1 to D64, as predicted by the metabolome at D1, was highly correlated with the observed value. This study provided a proof of concept for metabolic characterization of the effect of ld\u2010IL\u20102 in ALS. These data could present advances toward a personalized medicine approach and present pharmacometabolomics as a key tool to complement genomic and transcriptional data for drug characterization, leading to systems pharmacology.\n                  <\/jats:p>","DOI":"10.1111\/nyas.15147","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T12:33:39Z","timestamp":1716294819000},"page":"82-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacometabolomics applied to low\u2010dose interleukin\u20102 treatment in amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"1536","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8788-2773","authenticated-orcid":false,"given":"Hugo","family":"Alarcan","sequence":"first","affiliation":[{"name":"Service de Biochimie et Biologie Mol\u00e9culaire CHRU Bretonneau  Tours France"},{"name":"UMR 1253 iBrain Universit\u00e9 de Tours, Inserm  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