{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:16:16Z","timestamp":1790806576438,"version":"4.1.0"},"reference-count":29,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.ymthe.2021.03.019","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T03:59:32Z","timestamp":1616817572000},"page":"2378-2386","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":57,"title":["Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II: A phase 2 trial in Brazil"],"prefix":"10.1016","volume":"29","author":[{"given":"Roberto","family":"Giugliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairei","family":"So","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyoshi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Yamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Tanizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sonoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-8643","authenticated-orcid":false,"given":"Yuji","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2021.03.019_bib1","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1073\/pnas.87.21.8531","article-title":"Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA","volume":"87","author":"Wilson","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2021.03.019_bib2","series-title":"Lysosomal Storage Disorders: A Practical Guide","first-page":"94","article-title":"The mucopolysaccharidoses","author":"Giuliani","year":"2012"},{"key":"10.1016\/j.ymthe.2021.03.019_bib3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S2352-4642(17)30087-1","article-title":"Neurological manifestations of lysosomal disorders and emerging therapies targeting the CNS","volume":"2","author":"Giugliani","year":"2018","journal-title":"Lancet Child Adolesc. Health"},{"key":"10.1016\/j.ymthe.2021.03.019_bib4","doi-asserted-by":"crossref","first-page":"E400","DOI":"10.3390\/ijms21020400","article-title":"Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses","volume":"21","author":"Sato","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2021.03.019_bib5","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/01.gim.0000232477.37660.fb","article-title":"A phase II\/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)","volume":"8","author":"Muenzer","year":"2006","journal-title":"Genet. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ymgme.2006.09.001","article-title":"A phase I\/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome)","volume":"90","author":"Muenzer","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.03.019_bib7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ymgme.2009.08.006","article-title":"Japan Elaprase Treatment (JET) study: idursulfase enzyme replacement therapy in adult patients with attenuated Hunter syndrome (Mucopolysaccharidosis II, MPS II)","volume":"99","author":"Okuyama","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.03.019_bib8","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/GIM.0b013e3181fea459","article-title":"Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib9","doi-asserted-by":"crossref","first-page":"84ra44","DOI":"10.1126\/scitranslmed.3002230","article-title":"Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target","volume":"3","author":"Yu","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib10","doi-asserted-by":"crossref","first-page":"261ra154","DOI":"10.1126\/scitranslmed.3009835","article-title":"Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates","volume":"6","author":"Yu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1124\/dmd.111.042903","article-title":"Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse","volume":"40","author":"Zhou","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymthe.2021.03.019_bib12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuron.2013.10.061","article-title":"Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle","volume":"81","author":"Niewoehner","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2021.03.019_bib13","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1002\/bit.25289","article-title":"Insulin receptor antibody-iduronate 2-sulfatase fusion protein: pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys","volume":"111","author":"Boado","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymthe.2021.03.019_bib14","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13023-018-0849-8","article-title":"Neurocognitive and somatic stabilization in pediatric patients\u00a0with severe Mucopolysaccharidosis Type I after 52\u00a0weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein\u00a0(valanafusp alpha): an open label phase 1-2 trial","volume":"13","author":"Giugliani","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.ymthe.2021.03.019_bib15","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005338","article-title":"Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier","volume":"5","author":"Couch","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib16","first-page":"170105","article-title":"RefEx, a reference gene\u00a0expression dataset as a web tool for the functional analysis of genes","volume":"4","author":"Ono","year":"2017","journal-title":"Sci.\u00a0Data"},{"key":"10.1016\/j.ymthe.2021.03.019_bib17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.freeradbiomed.2018.06.037","article-title":"Transferrin and transferrin receptors update","volume":"133","author":"Kawabata","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/gim.2015.36","article-title":"A phase I\/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II","volume":"18","author":"Muenzer","year":"2016","journal-title":"Genet. Med."},{"key":"10.1016\/j.ymthe.2021.03.019_bib19","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/mt.2011.27","article-title":"Therapeutic potential of intracerebroventricular replacement of modified human \u03b2-hexosaminidase B for GM2 gangliosidosis","volume":"19","author":"Matsuoka","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.03.019_bib20","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1038\/s41467-018-04529-6","article-title":"Blood-brain barrier opening in Alzheimer\u2019s disease using MR-guided focused ultrasound","volume":"9","author":"Lipsman","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2021.03.019_bib21","doi-asserted-by":"crossref","first-page":"e0148613","DOI":"10.1371\/journal.pone.0148613","article-title":"Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier","volume":"11","author":"Leuthardt","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2021.03.019_bib23","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.ymthe.2018.02.032","article-title":"A Blood-Brain-Barrier-Penetrating Anti-human Transferrin Receptor Antibody Fusion Protein for Neuronopathic Mucopolysaccharidosis II","volume":"26","author":"Sonoda","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.03.019_bib24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ymgme.2018.07.013","article-title":"Evaluation of cerebrospinal fluid heparan sulfate\u00a0as a biomarker of neuropathology in a murine model of mucopolysaccharidosis type II using high-sensitivity LC\/MS\/MS","volume":"125","author":"Tanaka","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.03.019_bib25","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ymthe.2018.12.005","article-title":"Iduronate-2-Sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1\/2 Trial","volume":"27","author":"Okuyama","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.03.019_bib26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ymthe.2020.09.039","article-title":"A phase 2\/3\u00a0trial of pabinafusp alfa, IDS fused with anti-human transferrin receptor\u00a0antibody, targeting neurodegeneration in MPS-II","volume":"29","author":"Okuyama","year":"2021","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.03.019_bib27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ymgme.2017.09.007","article-title":"Assessments of neurocognitive and behavioral function in the mucopolysaccharidoses","volume":"122S","author":"Shapiro","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.03.019_bib28","volume":"Volume 1","author":"Bowlby","year":"1969"},{"key":"10.1016\/j.ymthe.2021.03.019_bib29","first-page":"100630","article-title":"Natural history of cognitive development in neuronopathic mucopolysaccharidosis type II (Hunter syndrome): Contribution of genotype to cognitive developmental course","volume":"24","author":"Seo","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"10.1016\/j.ymthe.2021.03.019_bib30","series-title":"A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II. ClinicalTrials.gov: NCT04573023","year":"2020"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621001489?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621001489?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:00:27Z","timestamp":1761501627000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001621001489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["S1525001621001489"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.03.019","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II: A phase 2 trial in Brazil","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.03.019","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s).","name":"copyright","label":"Copyright"}]}}