New insights into how vosoritide affects growth signaling in hypochondroplasia
A new study published in The Journal of Clinical Endocrinology & Metabolism provides insight into how vosoritide, a C-type natriuretic peptide (CNP) analog, affects growth-related biomarkers in children with hypochondroplasia (HCH), revealing a potential interaction between CNP signaling and insulin-like growth factor-1 (IGF-1).
“CNP analogs are novel therapeutics, and their interaction with other growth-promoting peptides has been largely uncharted territory,” said Roopa Shankar, MD, endocrinologist at Children’s National Hospital and lead author of the study.
What the study found
The phase 2 clinical trial followed 24 children with HCH who received daily vosoritide injections for one year. While vosoritide has been shown to promote height gain, little was previously known about its downstream effects on other growth-promoting peptides.
At baseline, children with HCH had elevated levels of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) and reduced IGF-1 levels. Following treatment with vosoritide, NTproCNP levels declined steadily over 12 months, while increases in IGF-1 were more delayed and variable.
Despite these different response patterns, changes from baseline in the two biomarkers at one year were positively correlated, suggesting a significant, and likely indirect, interaction between growth pathways.
The patient benefit
“These findings are promising and suggest that further study could help us better understand how the different growth signaling pathways interact in other genetic conditions where CNP analogs and growth hormone therapy may both be utilized in concert to improve growth outcomes,” said Dr. Shankar.
Children’s National leads the way
Children’s National is leading clinical trials of vosoritide across multiple genetic conditions, including hypochondroplasia, aggrecan mutations and Rasopathies, under the direction of Andrew Dauber, MD, MMSc, chief of Endocrinology. Additional studies in Turner syndrome are led by Dr. Shankar.
“This work positions us to better understand not only whether these therapies work, but how they work,” the researchers noted, “which is essential for advancing care for children with genetic growth disorders.”
Read the full study, Effect of Vosoritide Therapy on IGF-I and Endogenous C-Type Natriuretic Peptide in Hypochondroplasia, in The Journal of Clinical Endocrinology & Metabolism.
Other Children’s National authors include Andrew Dauber, MD, MMSc, Anqing Zhang, PhD, Niusha Shafaei, MSc, Kimberly Pitner, MSHS, BSN, RN, Raheem Seaforth.
