{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:11:49Z","timestamp":1772169109934,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.12431.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T00:00:00Z","timestamp":1522800000000}}],"reference-count":16,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T00:00:00Z","timestamp":1522800000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Parkinson\u2019s Disease UK"},{"name":"Wellcome Trust","award":["202834"],"award-info":[{"award-number":["202834"]}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Niemann-Pick Research Foundation"}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the\n                    <ns4:italic>NPC1<\/ns4:italic>\n                    or\n                    <ns4:italic>NPC2<\/ns4:italic>\n                    genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age.\n                  <\/ns4:p>\n                  <ns4:p\/>\n                  <ns4:p>We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and also in post-mortem liver from NPC patients. We demonstrated the ability of the hydrophobic bile acid ursodeoxycholic acid (UDCA) (3\u03b1, 7\u03b2-dihydroxy-5\u03b2-cholanic acid) to correct the P450 system suppression. UDCA is used to treat several cholestatic disorders and was tested in NPC due to the P450 system being regulated by bile acids. Here, we compare the effect of UDCA and cholic acid (CA), another bile acid, in the NPC mouse model. We observed unexpected hepatotoxicity in response to CA treatment of NPC mice. No such hepatotoxicity was associated with UDCA treatment. These results suggest that CA treatment is contraindicated in NPC patients, whilst supporting the use of UDCA as an adjunctive therapy in NPC patients.<\/ns4:p>","DOI":"10.12688\/wellcomeopenres.12431.2","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T11:35:27Z","timestamp":1522841727000},"page":"76","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C"],"prefix":"10.12688","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-630X","authenticated-orcid":false,"given":"Elena-Raluca","family":"Nicoli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-7110","authenticated-orcid":false,"given":"Mylene","family":"Huebecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9845-5913","authenticated-orcid":false,"given":"David","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-0403","authenticated-orcid":false,"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2018,4,4]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C.","volume":"5","author":"M Vanier","year":"2010","journal-title":"Orphanet J Rare Dis."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"41-48","DOI":"10.1038\/gim.2015.25","article-title":"High incidence of unrecognized visceral\/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets.","volume":"18","author":"C Wassif","year":"2016","journal-title":"Genet Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"869-81","DOI":"10.1194\/jlr.M600488-JLR200","article-title":"Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C 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Med."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"232-235","DOI":"10.1126\/science.277.5323.232","article-title":"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.","volume":"277","author":"S Loftus","year":"1997","journal-title":"Science."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1247-1255","DOI":"10.1038\/nm.1876","article-title":"Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium.","volume":"14","author":"E Lloyd-Evans","year":"2008","journal-title":"Nat Med."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"G494-502","DOI":"10.1152\/ajpgi.00156.2003","article-title":"Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse.","volume":"285","author":"D Wang","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"789-795","DOI":"10.1111\/j.1471-4159.2010.06976.x","article-title":"Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches.","volume":"116","author":"A Rosenbaum","year":"2011","journal-title":"J Neurochem."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"56ra81","DOI":"10.1126\/scitranslmed.3001417","article-title":"Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease.","volume":"2","author":"F Porter","year":"2010","journal-title":"Sci Transl Med."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"75","DOI":"10.12688\/wellcomeopenres.11854.1","article-title":"Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases [version 1; referees: 2 approved].","volume":"2","author":"W Evans","year":"2017","journal-title":"Wellcome Open 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Model of Niemann-Pick Disease Type C.","author":"F Platt","year":"2017","journal-title":"Open Science Framework."}],"container-title":["Wellcome Open 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.13461.r25792, Md Suhail Alam, Boler-Parseghian  Center for Rare and Neglected Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA, 19 Sep 2017, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-76\/v1#referee-response-25792","order":0,"name":"referee-response-25792","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.15584.r32737, Stephen D Turley, Southwestern Medical Center, University of Texas, Dallas, TX, USA, 19 Apr 2018, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-76\/v2#referee-response-32737","order":1,"name":"referee-response-32737","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.13461.r26337, Roberto Giugliani, National Institute on Population Medical Genetics - INAGEMP, Porto Alegre, Brazil, 12 Oct 2017, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-76\/v1#referee-response-26337","order":2,"name":"referee-response-26337","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [202834] to FP; Action Medical Research to ERN; Parkinson\u2019s Disease UK to MH; Niemann-Pick Research Foundation to DS and LM; Royal Society Wolfson Research Merit Award to FP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}