| Title: |
Pharmacometabolomics applied to low‐dose interleukin‐2 treatment in amyotrophic lateral sclerosis |
| Authors: |
Alarcan, H.; Bruno, C.; Emond, P.; Raoul, C.; Vourc'h, P.; Corcia, P.; Camu, W.; Veyrune, J.; Garlanda, C.; Locati, M.; Juntas‐Morales, R.; Saker, S.; Suehs, C.; Masseguin, C.; Kirby, J.; Shaw, P.; Malaspina, A.; De Vos, J.; Al‐Chalabi, A.; Leigh, P.N.; Tree, T.; Bensimon, G.; Blasco, H. |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
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 |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0077-8923 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/212822/1/Annals%20of%20the%20New%20York%20Academy%20of%20Sciences%20-%202024%20-%20Alarcan%20-%20Pharmacometabolomics%20applied%20to%20low%E2%80%90dose%20interleukin%E2%80%902%20%281%29.pdf; Alarcan, H. orcid.org/0009-0002-8788-2773 , Bruno, C., Emond, P. et al. (20 more authors) (2024) Pharmacometabolomics applied to low‐dose interleukin‐2 treatment in amyotrophic lateral sclerosis. Annals of the New York Academy of Sciences, 1536 (1). pp. 82-91. ISSN: 0077-8923 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/212822/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.E7B4536F |
| Database: |
BASE |