Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients.
Duchenne muscular dystrophy
RNA-seq
biomarkers
dystrophinopathies
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
09 04 2021
09 04 2021
Historique:
revised:
09
02
2021
received:
24
08
2020
accepted:
10
02
2021
pubmed:
23
3
2021
medline:
26
10
2021
entrez:
22
3
2021
Statut:
ppublish
Résumé
DMD is a rare disorder characterized by progressive muscle degeneration and premature death. Therapy development is delayed by difficulties to monitor efficacy non-invasively in clinical trials. In this study, we used RNA-sequencing to describe the pathophysiological changes in skeletal muscle of 3 dystrophic mouse models. We show how dystrophic changes in muscle are reflected in blood by analyzing paired muscle and blood samples. Analysis of repeated blood measurements followed the dystrophic signature at five equally spaced time points over a period of seven months. Treatment with two antisense drugs harboring different levels of dystrophin recovery identified genes associated with safety and efficacy. Evaluation of the blood gene expression in a cohort of DMD patients enabled the comparison between preclinical models and patients, and the identification of genes associated with physical performance, treatment with corticosteroids and body measures. The presented results provide evidence that blood RNA-sequencing can serve as a tool to evaluate disease progression in dystrophic mice and patients, as well as to monitor response to (dystrophin-restoring) therapies in preclinical drug development and in clinical trials.
Identifiants
pubmed: 33751844
doi: 10.15252/emmm.202013328
pmc: PMC8033515
doi:
Banques de données
GEO
['GSE132741']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13328Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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