C-Type Natriuretic Peptide (CNP)
A natriuretic peptide found primarily in the brain and vascular endothelium that also plays a critical role in bone growth. Vosoritide is a CNP analogue that acts on growth plate cartilage to counteract the growth-inhibiting effects of FGFR3 mutations in achondroplasia, enabling increased linear growth in children.
Technical Context
CNP exists in two forms: CNP-22 (22 aa) and CNP-53 (53 aa, N-terminally extended). CNP activates NPR-B (not NPR-A like ANP/BNP), generating cGMP that activates PKG-II in growth plate chondrocytes. PKG-II inhibits the RAF-MEK-ERK (MAPK) signalling pathway downstream of FGFR3 — the constitutively active receptor in achondroplasia. By counteracting FGFR3 signalling, CNP promotes chondrocyte proliferation and hypertrophy, enabling longitudinal bone growth. Vosoritide (BMN 111) is a 39 amino acid CNP analogue with improved stability (half-life ~30 minutes vs ~3 minutes for CNP-22). Daily subcutaneous vosoritide injection produced sustained increases in annualised growth velocity (mean gain ~1.5 cm/year over placebo) in children with achondroplasia.