Evidence of feedback regulation of C-type natriuretic peptide during Vosoritide therapy in Achondroplasia.

Prickett TCR, Espiner EA, Irving M, Bacino C, Phillips JA 3rd, Savarirayan R, Day JRS, Fisheleva E, Larimore K, Chan ML, Jeha GS

Scientific reports20 Dec 2021Cited by 4 (Europe PMC)

PMID34930956PMCIDPMC8688426DOI10.1038/s41598-021-03593-1PepBankPUB-34930956

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Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanNon-randomized trialActivity measurement
In children with achondroplasia receiving vosoritide, age- and sex-adjusted NTproCNP SDS significantly decreased within the first 3 months of accelerating growth.
In plain wordsIn children receiving vosoritide, adjusted NTproCNP scores significantly decreased from pretreatment values within the first 3 months of accelerating growth.
Peptide
Vosoritide
Outcome
DecreaseNTproCNP during initial growth acceleration
Study
n = 28
Comparator
Before treatment
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Studied dose
Dose not stated
Source sentences
Summary
Within the first 3 months of accelerating growth, levels were significantly reduced.
2 context sentences(design, population, supporting numbers)
Summary · context
Before treatment NTproCNP SDS was raised.
Summary · context
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.
Show in the study text Report a problemFND-3493095601
02HumanNon-randomized trialActivity measurement
In children receiving vosoritide, age- and sex-adjusted NTproCNP SDS varied widely across 5 years and increased markedly in some subjects during adolescence.
In plain wordsIn children receiving vosoritide, adjusted NTproCNP scores varied across 5 years and increased markedly in some subjects during adolescence.
Peptide
Vosoritide
Outcome
MixedNTproCNP during sustained growth
Study
n = 28
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Studied dose
Dose not stated · 5 yearsAs given in this study (human).
Source sentences
Summary
Across the 5 years of sustained growth, levels varied widely and were markedly increased in some subjects during adolescence.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3493095602
03HumanObservational studyActivity measurement
In children receiving vosoritide, plasma NTproCNP was suppressed at 4 h post-injection in proportion to pre-injection hormone resistance.
In plain wordsIn children receiving vosoritide, NTproCNP decreased at 4 h after injection in proportion to pre-injection hormone resistance.
Peptide
Vosoritide
Outcome
DecreaseNTproCNP after injection
Study
n = 28
Comparator
Before injection
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Studied dose
Dose not stated
Source sentences
Summary
Plasma NTproCNP was suppressed at 4 h post-injection in proportion to the prevailing level of hormone resistance as reflected by SDS before injection.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3493095603

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Version history

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Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

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