| Title: |
Pharmacometabolomics applied to low-dose interleukin-2 treatment in amyotrophic lateral sclerosis |
| Authors: |
Alarcan, Hugo; Bruno, Clément; Emond, Patrick; Raoul, Cédric; Vourc’h, Patrick; Corcia, Philippe; Camu, William; Veyrune, Jean‐luc; Garlanda, Cecilia; Locati, Massimo; Juntas‐morales, Raúl; Saker, Safaa; Suehs, Carey; Masseguin, Christophe; Kirby, Janine; Shaw, Pamela; Malaspina, Andrea; de Vos, John; Al-Chalabi, Ammar; Leigh, P, Nigel; Tree, Timothy; Bensimon, Gilbert; Blasco, Hélène |
| Contributors: |
Imaging, Brain & Neuropsychiatry (iBraiN); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Institut des Neurosciences de Montpellier (INM); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Institut de génétique humaine (IGH); Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Humanitas University Milan (Hunimed); Humanitas Clinical and Research Center Rozzano, Milan, Italy; Vall d'Hebron University Hospital Barcelona; Généthon; Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie CHU Nîmes (BESPIM); Hôpital Universitaire Carémeau Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Nîmes (CHU Nîmes); University of Sheffield Sheffield; The Institute of Neuroscience Sheffield; University College London UCL (UCL); Université de Montpellier (UM); Maurice Wohl Clinical Neuroscience Institut; King‘s College London; Brighton and Sussex Medical School (BSMS); National Institute of Health and Medical Research |
| Source: |
ISSN: 0077-8923. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2024 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
metabolomics; pharma- cometabolomics; kynurenine pathway; interleukin-2; amyotrophic lateral sclerosis; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low-dose (ld) interleukin-2 (IL-2). We propose a pharmacometabolomics approach to decipher metabolic modifications occurring in patients treated with ld-IL-2 and its relationship with Treg response. Blood metabolomic profiles were determined on days D1, D64, and D85 from patients receiving 2 MIU of IL-2 (n = 12) and patients receiving a placebo (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-IL-2 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38771698; PUBMED: 38771698 |
| DOI: |
10.1111/nyas.15147 |
| Availability: |
https://hal.science/hal-04767126; https://hal.science/hal-04767126v1/document; https://hal.science/hal-04767126v1/file/Ann%20N%20Y%20Acad%20Sci%202024.pdf; https://doi.org/10.1111/nyas.15147 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.5F329CA9 |
| Database: |
BASE |