{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:42:58Z","timestamp":1784641378831,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T00:00:00Z","timestamp":1414627200000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL009610"],"award-info":[{"award-number":["R01HL009610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In Niemann\u2013Pick type C (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) disease, loss\u2010of\u2010function mutations in either <jats:italic><jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>1<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>2<\/jats:italic> result in progressive accumulation of unesterified cholesterol (<jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>) and glycosphingolipids in all organs, leading to neurodegeneration, pulmonary dysfunction and sometimes liver failure. There is no cure for this disorder. Studies using primarily <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> mouse models have shown that systemic administration of 2\u2010hydroxypropyl\u2010\u03b2\u2010cyclodextrin (2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>), starting in early neonatal life, diminishes <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content> accumulation in most organs, slows disease progression and extends lifespan. The key question now is whether delaying the start of 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> treatment until early adulthood, when the amount of entrapped <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content> throughout the body is markedly elevated, has any of the benefits found when treatment begins at 7\u00a0days of age. In the present study, <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice were given saline or 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> subcutaneously at 49, 56, 63 and 70\u00a0days of age, with measurements of organ weights, liver function tests and tissue cholesterol levels performed at 77\u00a0days. In <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, treatment with 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> from 49\u00a0days reduced whole\u2010liver cholesterol content at 77\u00a0days from 33.0\u00a0\u00b1\u00a01.0 to 9.1\u00a0\u00b1\u00a00.5\u00a0mg\/organ. Comparable improvements were seen in other organs, such as the spleen, and in the animal as a whole. There was a transient increase in biliary cholesterol concentration in <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice after 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>. Plasma alanine aminotransferase and aspartate aminotransferase activities in 77\u2010day\u2010old 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\u2010treated <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were reduced compared with saline\u2010treated controls. The lifespan of <jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice given 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> marginally exceeded that of the saline\u2010treated controls (99\u00a0\u00b1\u00a01.1 <jats:italic>vs<\/jats:italic> 94\u00a0\u00b1\u00a01.4\u00a0days, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Thus, 2<jats:styled-content style=\"fixed-case\">HP<\/jats:styled-content>\u03b2<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> is effective in mobilizing entrapped cholesterol in late\u2010stage <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> disease leading to improved liver function.<\/jats:p>","DOI":"10.1111\/1440-1681.12285","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T12:37:44Z","timestamp":1407847064000},"page":"780-787","source":"Crossref","is-referenced-by-count":36,"title":["Systemic administration of 2\u2010hydroxypropyl\u2010\u03b2\u2010cyclodextrin to symptomatic Npc1\u2010deficient mice slows cholesterol sequestration in the major organs and improves liver function"],"prefix":"10.1111","volume":"41","author":[{"given":"Adam M","family":"Lopez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandi J","family":"Terpack","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charina M","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Turley","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-16"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112751108"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-012-0130-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2009.034.04.1352412"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/clp.12.31"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R047837"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70194-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810895106"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M000257"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181ee4dd2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1317-11.2011"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M013789"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600488-JLR200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/S0022-2275(20)42344-2","article-title":"Lysosomal acid lipase deficiency in rats. 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