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Nat Commun. 2015 Dec 1;6:10006. doi: 10.1038/ncomms10006.

ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.

Author information

1
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
3
Alexion, Cheshire, Connecticut 06410, USA.
4
Department of Medicine and Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
5
WM Keck Biotechnology Research Laboratory, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
6
Biotechnology Core Laboratory, National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
7
Z-Concepts LLC, East Haven, Connecticut 06512, USA.

Abstract

Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification.

PMID:
26624227
PMCID:
PMC4686714
DOI:
10.1038/ncomms10006
[Indexed for MEDLINE]
Free PMC Article

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