{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:51:54Z","timestamp":1776199914020,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Metakids, Hersenstichting","award":["F 2012(1)-102)"],"award-info":[{"award-number":["F 2012(1)-102)"]}]},{"name":"Axel Foundation"},{"name":"Stichting Steun Emma Kinderziekenhuis AMC, the Netherlands"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C<jats:sub>27<\/jats:sub>\u2010bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. It was noted that, in patients with advanced liver disease, caution is needed because of possible hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An extension study of the previously conducted pretest\u2010posttest design study was conducted including 17 patients with a ZSD. All patients received oral CA for an additional period of 12\u2009months, encompassing a total of 21\u2009months of treatment. Multiple clinically relevant parameters and markers for bile acid synthesis were assessed after 15 and 21\u2009months of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bile acid synthesis was still suppressed after 21\u2009months of CA treatment, accompanied with reduced levels of C<jats:sub>27<\/jats:sub>\u2010bile acid intermediates in plasma. These levels significantly increased again after discontinuation of CA. No significant changes were found in liver tests, liver elasticity, coagulation parameters, fat\u2010soluble vitamin levels or body weight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although CA treatment did lead to reduced levels of toxic C<jats:sub>27<\/jats:sub>\u2010bile acid intermediates in ZSD patients without severe liver fibrosis or cirrhosis, no improvement of clinically relevant parameters was observed after 21\u2009months of treatment. We discuss the implications for CA therapy in ZSD based on these results.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jimd.12042","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T04:16:09Z","timestamp":1550808969000},"page":"303-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy"],"prefix":"10.1002","volume":"42","author":[{"given":"Femke C. C.","family":"Klouwer","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center University of Amsterdam, Meibergdreef 9, 1105 AZ  Amsterdam The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart G. 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