{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:40:57Z","timestamp":1790779257251,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibres in the skin, eyes and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently, no specific treatment exists to counteract the progression of symptoms. PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in <jats:italic>ABCC6<\/jats:italic>, <jats:italic>ENPP1<\/jats:italic> and <jats:italic>NT5E<\/jats:italic> are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PP<jats:sub>i<\/jats:sub>) concentration in the circulation. Although PP<jats:sub>i<\/jats:sub> is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na<jats:sub>4<\/jats:sub>P<jats:sub>2<\/jats:sub>O<jats:sub>7<\/jats:sub> is absorbed in humans. Here, we report that gelatin\u2010encapsulated Na<jats:sub>2<\/jats:sub>H<jats:sub>2<\/jats:sub>P<jats:sub>2<\/jats:sub>O<jats:sub>7<\/jats:sub>\u00a0has similar absorption properties in healthy volunteers and people affected by PXE. The sodium\u2010free K<jats:sub>2<\/jats:sub>H<jats:sub>2<\/jats:sub>P<jats:sub>2<\/jats:sub>O<jats:sub>7<\/jats:sub> form resulted in similar uptake in healthy volunteers and inhibited calcification in <jats:italic>Abcc6<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step towards testing oral PP<jats:sub>i<\/jats:sub> in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing.<\/jats:p>","DOI":"10.1111\/exd.14498","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T20:51:05Z","timestamp":1636577465000},"page":"548-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-3752","authenticated-orcid":false,"given":"Eszter","family":"Koz\u00e1k","sequence":"first","affiliation":[{"name":"Institute of Enzymology Research Centre for Natural Sciences Hungarian Academy of Sciences Centre of Excellence  Budapest 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Sciences Hungarian Academy of Sciences Centre of Excellence  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8495-7103","authenticated-orcid":false,"given":"Qiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology PXE International Center of Excellence in Research and Clinical Care Sidney Kimmel Medicine College Jefferson Institute of Molecular Medicine Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-9329","authenticated-orcid":false,"given":"Sharon F.","family":"Terry","sequence":"additional","affiliation":[{"name":"PXE International  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-807X","authenticated-orcid":false,"given":"Jouni","family":"Uitto","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology PXE International Center of Excellence in Research and Clinical Care Sidney Kimmel Medicine College Jefferson Institute of Molecular Medicine Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Theratrophix  Sunnyvale California USA"},{"name":"Pyrogenyx  Sunnyvale California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-464X","authenticated-orcid":false,"given":"Cyrus","family":"Becker","sequence":"additional","affiliation":[{"name":"Theratrophix  Sunnyvale California USA"},{"name":"Pyrogenyx  Sunnyvale California 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