{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:28:06Z","timestamp":1769074086685,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T00:00:00Z","timestamp":1433894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR000004"],"award-info":[{"award-number":["UL1 TR000004"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>The primary treatment outcomes of a phase 2, randomized, double\u2010blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged \u22657 years and able to walk \u2265200\u2009m in the 6\u2010min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0\u2009mg\/kg\/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3\u2010min stair climb test [3MSCT]), exercise capacity (cardio\u2010pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty\u2010five patients were enrolled (15 randomized to 2.0\u2009mg\/kg\/week and 10 to 4.0\u2009mg\/kg\/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0\u2009mg\/kg\/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0\u20134.0\u2009mg\/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0\u2009mg\/kg\/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. \u00a9 2015 The Authors. <jats:italic>American Journal of Medical Genetics Part A<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37172","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T03:26:02Z","timestamp":1433993162000},"page":"2272-2281","source":"Crossref","is-referenced-by-count":34,"title":["Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double\u2010blind, pilot study"],"prefix":"10.1002","volume":"167","author":[{"given":"Barbara K.","family":"Burton","sequence":"first","affiliation":[{"name":"Ann and Robert H. Lurie Children's Hospital Chicago Illinois"},{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth I.","family":"Berger","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"McMaster University Medical Center Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsha","family":"Treadwell","sequence":"additional","affiliation":[{"name":"UCSF Benioff Children's Hospital Oakland Oakland California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Montreal Children's Hospital Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Muschol","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Willink Unit St. Mary's Hospital, CMFT, MAHSC University of Manchester Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. Reid","family":"Sutton","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital Houston Texas"},{"name":"Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory M.","family":"Pastores","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"},{"name":"Mater Misericordiae University Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Lau","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sparkes","sequence":"additional","affiliation":[{"name":"Alberta Children's Hospital Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Genter","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam J.","family":"Shaywitz","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Harmatz","sequence":"additional","affiliation":[{"name":"UCSF Benioff Children's Hospital Oakland Oakland California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.12.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.021"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.11.076"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9459-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s10545-014-9715-6","article-title":"STRIVE Investigators. 2014a Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): A phase 3 randomised placebo\u2010controlled study","volume":"37","author":"Hendriksz CJ","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-32"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36833"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.08.012"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2013.09.006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmn.2013.03.002"},{"key":"e_1_2_6_13_1","article-title":"Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 years","author":"Jones SA","year":"2015","journal-title":"J Pediatr"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2007.123653"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-883OC"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-84"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00034805"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000232477.37660.fb"},{"key":"e_1_2_6_19_1","article-title":"Immunogenicity of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A syndrome: Results from MOR\u2010004, a phase 3 trial","author":"Schweighardt B","year":"2014","journal-title":"Clinical Therapeutics"},{"key":"e_1_2_6_20_1","volume-title":"Applied biopharmaceutics and pharmacokinetics","author":"Shargel L","year":"2005"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920111795542615"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.01.046"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.04.009"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37172","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T11:10:51Z","timestamp":1694344251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,10]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1002\/ajmg.a.37172"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37172","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,10]]}}}