{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:54:03Z","timestamp":1790420043213,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"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":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis (MPS) disorders are a group of rare, progressive lysosomal storage diseases characterized by the accumulation of glycosaminoglycans (GAGs) and classified according to the deficient enzyme. Enzyme replacement therapy (ERT) of MPS VI has limited effects on ophthalmic, cardiovascular, and skeletal systems. Odiparcil is an orally available small molecule that results in the synthesis of odiparcil\u2010linked GAGs facilitating their excretion and reducing cellular and tissue GAG accumulation. <jats:italic>Improve MPS treatment<\/jats:italic> was a Phase 2a study of the safety, pharmacokinetics\/pharmacodynamics, and efficacy of two doses of odiparcil in patients with MPS VI. The core study was a 26\u2010week, randomized, double\u2010blind, placebo\u2010controlled trial in patients receiving ERT and an open\u2010label, noncomparative, single\u2010dose cohort not receiving ERT. Patients aged \u2265\u200916\u2009years receiving ERT were randomized to odiparcil 250 or 500\u2009mg twice daily or placebo. Patients without ERT received odiparcil 500\u2009mg twice daily. Of 20 patients enrolled, 13 (65.0%) completed the study. Odiparcil increased total urine GAGs (uGAGs), chondroitin sulfate, and dermatan sulfate concentrations. A linear increase in uGAG levels and odiparcil exposure occurred with increased odiparcil dose. Odiparcil demonstrated a good safety and tolerability profile. Individual analyses found more improvements in pain, corneal clouding, cardiac, vascular, and respiratory functions in the odiparcil groups vs placebo. This study confirmed the mechanism of action and established the safety of odiparcil with clinical beneficial effects after only a short treatment duration in an advanced stage of disease. Further assessment of odiparcil in younger patients is needed.<\/jats:p>","DOI":"10.1002\/jimd.12467","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T14:27:39Z","timestamp":1639578459000},"page":"340-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oral treatment for mucopolysaccharidosis <scp>VI<\/scp>: Outcomes of the first phase <scp>IIa<\/scp> study with odiparcil"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3052-2366","authenticated-orcid":false,"given":"Nathalie","family":"Guffon","sequence":"first","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme, Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Le\u00e3o","family":"Teles","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derralynn","family":"Hughes","sequence":"additional","affiliation":[{"name":"Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, Department of Pediatric and Adolescent Medicine University Medical Center Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Huot\u2010Marchand","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Faudot\u2010Vernier","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fiquet","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Paule","family":"Richard","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Abitbol","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Tallandier","sequence":"additional","affiliation":[{"name":"Inventiva  Daix France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Hendriksz","sequence":"additional","affiliation":[{"name":"Steve Biko Academic Unit University of Pretoria  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"245","article-title":"Diagnostic and treatment strategies in mucopolysaccharidosis VI","volume":"8","author":"Vairo F","year":"2015","journal-title":"Appl Clin Genet"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-5"},{"key":"e_1_2_10_4_1","first-page":"3421","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld EF","year":"2001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2184"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.12.014"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.04.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-9007-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36584"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1080-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1023"},{"key":"e_1_2_10_12_1","article-title":"Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI","volume":"3","author":"Brunelli MJ","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082975"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.03.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008323751"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0233032"},{"issue":"21","key":"e_1_2_10_17_1","article-title":"MPS VI associated ocular phenotypes in an MPS VI murine model and the therapeutic effects of odiparcil treatment","volume":"1096","author":"Entchev E","year":"2021","journal-title":"Mol Genet Metab"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.09.009"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1836-9553(10)70049-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663792"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20647"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.11.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/20.6.649"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520460115022"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30579"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9410-9"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_333"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12467","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12467","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T01:21:48Z","timestamp":1692753708000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,30]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/jimd.12467"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12467","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,30]]},"assertion":[{"value":"2021-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}