Pharmacometabolomics applied to low-dose interleukin-2 treatment in amyotrophic lateral sclerosis.
Ann N Y Acad Sci
; 1536(1): 82-91, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38771698
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Interleucina-2
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Linfócitos T Reguladores
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Metabolômica
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Esclerose Lateral Amiotrófica
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article