Evidence of feedback regulation of C-type natriuretic peptide during Vosoritide therapy in Achondroplasia.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 12 2021
20 12 2021
Historique:
received:
26
07
2021
accepted:
03
12
2021
entrez:
21
12
2021
pubmed:
22
12
2021
medline:
26
2
2022
Statut:
epublish
Résumé
Evidence from genetic disorders of CNP signalling suggests that plasma concentrations of CNP are subject to feedback regulation. In subjects with Achondroplasia (Ach), CNP intracellular activity is suppressed and plasma concentrations are raised but the therapeutic impact of exogenous CNP agonists on endogenous CNP is unknown. In this exploratory dose finding and extension study of 28 Ach children receiving Vosoritide over a 5 year period of treatment, endogenous CNP production was assessed using measurements of plasma aminoterminal proCNP (NTproCNP) adjusted for age and sex and normalised as standard deviation score (SDS), and then related to skeletal growth. Before treatment NTproCNP SDS was raised. Within the first 3 months of accelerating growth, levels were significantly reduced. Across the 5 years of sustained growth, levels varied widely and were markedly increased in some subjects during adolescence. Plasma NTproCNP was suppressed at 4 h post-injection in proportion to the prevailing level of hormone resistance as reflected by SDS before injection. We conclude CNP remains subject to regulation during growth promoting doses of Vosoritide. Fall in CNP during accelerating growth is consistent with an indirect feedback whereas the fall at 4 h is likely to be a direct effect from removal of intra cellular CNP resistance.
Identifiants
pubmed: 34930956
doi: 10.1038/s41598-021-03593-1
pii: 10.1038/s41598-021-03593-1
pmc: PMC8688426
doi:
Substances chimiques
Natriuretic Peptide, C-Type
127869-51-6
vosoritide
7SE5582Q2P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24278Informations de copyright
© 2021. The Author(s).
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