INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6^-/- mouse model of pseudoxanthoma elasticum.

ABSTRACT: Pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic calcification disorder, is predominantly caused by inactivating mutations in ABCC6. The encoded protein, ABCC6, is a hepatic efflux transporter and a key regulator of extracellular inorganic pyrophosphate (PPi). Recent studies demonstrated that deficiency of plasma PPi, a potent endogenous calcification inhibitor, is the underlying cause of PXE. This study examined whether restoring plasma PPi levels by INZ-701, a recombinant human ENPP1 protein, the principal PPi-generating enzyme, prevents ectopic calcification in an Abcc6^-/- mouse model of PXE. Abcc6^-/- mice, at 6 weeks of age, the time of earliest stages of ectopic calcification, were injected subcutaneously with INZ-701 at 2 or 10 mg/kg for 2 or 8 we

SUBMITTER: Jacobs IJ 

PROVIDER: S-EPMC10077110 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature