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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\u2010701, a recombinant human ENPP1 protein, the principal PPi\u2010generating enzyme, prevents ectopic calcification in an <jats:italic>Abcc6<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mouse model of PXE. <jats:italic>Abcc6<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, at 6\u2009weeks of age, the time of earliest stages of ectopic calcification, were injected subcutaneously with INZ\u2010701 at 2 or 10\u00a0mg\/kg for 2 or 8\u2009weeks. INZ\u2010701 at both doses increased steady\u2010state plasma ENPP1 activity and PPi levels. In the 8\u2010week treatment study, histopathologic examination and quantification of the calcium content in INZ\u2010701\u2010treated <jats:italic>Abcc6<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice revealed significantly reduced calcification in the muzzle skin containing vibrissae, a biomarker of the calcification process in these mice. The extent of calcification corresponds to the local expression of two calcification inhibitors, osteopontin and fetuin\u2010A. These results suggest that INZ\u2010701 might provide a therapeutic approach for PXE, a disease with high unmet needs and no approved treatment.<\/jats:p>","DOI":"10.1111\/exd.14587","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T16:58:32Z","timestamp":1651769912000},"page":"1095-1101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>INZ<\/scp>\u2010701, a recombinant <scp>ENPP1<\/scp> enzyme, prevents ectopic calcification in an <i>Abcc6<\/i><sup>\u2212\/\u2212<\/sup> mouse model of pseudoxanthoma elasticum"],"prefix":"10.1111","volume":"31","author":[{"given":"Ida Joely","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine Thomas Jefferson University  Philadelphia Pennsylvania USA"},{"name":"PXE International Center of Excellence in Research 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