Response of plasma microRNAs to nusinersen treatment in patients with SMA.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
26
04
2022
received:
23
02
2022
accepted:
28
04
2022
pubmed:
19
5
2022
medline:
14
7
2022
entrez:
18
5
2022
Statut:
ppublish
Résumé
Spinal muscular atrophy (SMA) is a common genetic cause of infant mortality. Nusinersen treatment ameliorates the clinical outcome of SMA, however, some patients respond well, while others have limited response. We investigated microRNAs in blood samples from SMA patients and their response to nusinersen treatment evaluating the potential of circulating microRNAs as biomarkers for SMA. In a discovery cohort study, microRNA next-generation sequencing was performed in blood samples from SMA patients (SMA type 2, n = 10; SMA type 3, n = 10) and controls (n = 7). The dysregulated microRNAs were further analysed in the therapeutic response cohort comprised of SMA type 1 patients (n = 22) who had received nusinersen treatment, at three time points along the treatment course (baseline, 2 and 6 months of treatment). The levels of the studied microRNAs were correlated to the SMA clinical outcome measures. In the discovery cohort, 69 microRNAs were dysregulated between SMA patients and controls. In the therapeutic response cohort, the baseline plasma levels of miR-107, miR-142-5p, miR-335-5p, miR-423-3p, miR-660-5p, miR-378a-3p and miR-23a-3p were associated with the 2 and 6 months response to nusinersen treatment. Furthermore, the levels of miR-107, miR-142-5p, miR-335-5p, miR-423-3p, miR-660-5p and miR-378-3p at 2 months of treatment were associated with the response after 6 months of nusinersen treatment. Blood microRNAs could be used as biomarkers to indicate SMA patients' response to nusinersen and to monitor the efficacy of the therapeutic intervention. In addition, some of these microRNAs provide insight into processes involved in SMA that could be exploited as novel therapeutic targets.
Identifiants
pubmed: 35584175
doi: 10.1002/acn3.51579
pmc: PMC9268869
doi:
Substances chimiques
Biomarkers
0
MIRN660 microRNA, human
0
MicroRNAs
0
Oligonucleotides
0
nusinersen
5Z9SP3X666
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1011-1026Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204841/Z/16/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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