{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:11:40Z","timestamp":1790820700421,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.ymthe.2021.01.027","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T21:53:03Z","timestamp":1611611583000},"page":"1853-1861","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice"],"prefix":"10.1016","volume":"29","author":[{"given":"Hideto","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiho","family":"Kida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Yoden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Koshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Hirato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-6250","authenticated-orcid":false,"given":"Kohtaro","family":"Minami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sonoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2021.01.027_bib1","series-title":"The Metabolic & Molecular Bases of Inherited Disease","first-page":"3421","article-title":"The Mucopolysaccharidoses","author":"Neufeld","year":"2001"},{"issue":"Suppl 1","key":"10.1016\/j.ymthe.2021.01.027_bib2","first-page":"107","article-title":"Mucopolysaccharidosis type II, Hunter\u2019s syndrome","volume":"12","author":"Tylki-Szyma\u0144ska","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"10.1016\/j.ymthe.2021.01.027_bib3","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.2021.01.027_bib4","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/cge.12927","article-title":"Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II","volume":"91","author":"Dvorakova","year":"2017","journal-title":"Clin. Genet."},{"key":"10.1016\/j.ymthe.2021.01.027_bib5","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/dmcn.13467","article-title":"Genotype-phenotype relationship in mucopolysaccharidosis II: predictive power of IDS variants for the neuronopathic phenotype","volume":"59","author":"Vollebregt","year":"2017","journal-title":"Dev. Med. Child Neurol."},{"key":"10.1016\/j.ymthe.2021.01.027_bib6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/GIM.0b013e318206786f","article-title":"Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"10.1016\/j.ymthe.2021.01.027_bib7","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.2021.01.027_bib8","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1210\/edrv-7-3-314","article-title":"Receptor-mediated peptide transport through the blood-brain barrier","volume":"7","author":"Pardridge","year":"1986","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.ymthe.2021.01.027_bib9","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/0026-0495(87)90099-0","article-title":"Human blood-brain barrier transferrin receptor","volume":"36","author":"Pardridge","year":"1987","journal-title":"Metabolism"},{"key":"10.1016\/j.ymthe.2021.01.027_bib10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0169-409X(00)00139-3","article-title":"Delivery of peptides and proteins through the blood-brain barrier","volume":"46","author":"Bickel","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ymthe.2021.01.027_bib11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1517\/17425247.2014.952627","article-title":"Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody","volume":"12","author":"Pardridge","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"10.1016\/j.ymthe.2021.01.027_bib12","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/mt.2008.119","article-title":"Targeting of the CNS in MPS-IH using a nonviral transferrin-alpha-L-iduronidase fusion gene product","volume":"16","author":"Osborn","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.01.027_bib13","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.2021.01.027_bib14","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.2021.01.027_bib15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ymgme.2018.07.013","article-title":"Evaluation of cerebrospinal fluid heparan sulfate as 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.2021.01.027_bib16","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.2021.01.027_bib17","article-title":"A Phase 2\/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II","author":"Okuyama","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2021.01.027_bib18","first-page":"100455","article-title":"Biomarkers in patients with mucopolysaccharidosis type II and IV","volume":"19","author":"Fujitsuka","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"10.1016\/j.ymthe.2021.01.027_bib19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ymgme.2018.08.003","article-title":"Anatomical changes and pathophysiology of the brain in mucopolysaccharidosis disorders","volume":"125","author":"Bigger","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.01.027_bib20","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3390\/metabo4030655","article-title":"Establishment of glycosaminoglycan assays for mucopolysaccharidoses","volume":"4","author":"Tomatsu","year":"2014","journal-title":"Metabolites"},{"key":"10.1016\/j.ymthe.2021.01.027_bib21","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.mehy.2010.07.044","article-title":"Why are behaviors of children suffering from various neuronopathic types of mucopolysaccharidoses different?","volume":"75","author":"W\u0119grzyn","year":"2010","journal-title":"Med. Hypotheses"},{"key":"10.1016\/j.ymthe.2021.01.027_bib22","doi-asserted-by":"crossref","first-page":"400","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.2021.01.027_bib23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1750-1172-5-5","article-title":"Mucopolysaccharidosis VI","volume":"5","author":"Valayannopoulos","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.ymthe.2021.01.027_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2017.08.009","article-title":"Developmental and behavioral aspects of mucopolysaccharidoses with brain manifestations - Neurological signs and symptoms","volume":"122S","author":"Shapiro","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymthe.2021.01.027_bib25","series-title":"Mucopolysaccharidoses Update","first-page":"87","article-title":"Mechanisms of neurodegeneration in mucopolysaccharidoses","author":"W\u0119grzyn","year":"2018"},{"key":"10.1016\/j.ymthe.2021.01.027_bib26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-neuro-080317-061804","article-title":"Lysosomes and Brain Health","volume":"41","author":"Sharma","year":"2018","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1016\/j.ymthe.2021.01.027_bib27","doi-asserted-by":"crossref","first-page":"e906","DOI":"10.1038\/cddis.2013.430","article-title":"Murine neural stem cells model Hunter disease in\u00a0vitro: glial cell-mediated neurodegeneration as a possible mechanism involved","volume":"4","author":"Fusar Poli","year":"2013","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ymthe.2021.01.027_bib28","doi-asserted-by":"crossref","first-page":"e2331","DOI":"10.1038\/cddis.2016.231","article-title":"Glial degeneration with oxidative damage drives neuronal demise in MPSII disease","volume":"7","author":"Zalfa","year":"2016","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ymthe.2021.01.027_bib29","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/clinchem\/43.8.1325","article-title":"Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated membrane protein LAMP-1 as a diagnostic marker","volume":"43","author":"Meikle","year":"1997","journal-title":"Clin. Chem."},{"key":"10.1016\/j.ymthe.2021.01.027_bib30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13023-015-0357-z","article-title":"The effects of intracisternal enzyme replacement versus sham treatment on central neuropathology in preclinical canine fucosidosis","volume":"10","author":"Kondagari","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.ymthe.2021.01.027_bib31","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1242\/dmm.025122","article-title":"A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease","volume":"9","author":"Wolf","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.ymthe.2021.01.027_bib32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0165-0173(01)00067-4","article-title":"Applications of the Morris water maze in the study of learning and memory","volume":"36","author":"D\u2019Hooge","year":"2001","journal-title":"Brain Res. Brain Res. Rev."},{"key":"10.1016\/j.ymthe.2021.01.027_bib33","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.omtm.2018.07.005","article-title":"Targeting Root Cause by Systemic scAAV9-hIDS Gene Delivery: Functional Correction and Reversal of Severe MPS II in Mice","volume":"10","author":"Fu","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2021.01.027_bib34","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.lfs.2010.09.004","article-title":"Assessment of spatial memory in mice","volume":"87","author":"Sharma","year":"2010","journal-title":"Life Sci."},{"key":"10.1016\/j.ymthe.2021.01.027_bib35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/ilar\/ilu013","article-title":"Assessing spatial learning and memory in rodents","volume":"55","author":"Vorhees","year":"2014","journal-title":"ILAR J."},{"key":"10.1016\/j.ymthe.2021.01.027_bib36","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.2021.01.027_bib37","doi-asserted-by":"crossref","first-page":"e30341","DOI":"10.1371\/journal.pone.0030341","article-title":"CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: implications for neurological outcomes of lysosomal storage disorder","volume":"7","author":"Calias","year":"2012","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2021.01.027_bib38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ymgme.2012.05.005","article-title":"Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II","volume":"107","author":"Higuchi","year":"2012","journal-title":"Mol. Genet. Metab."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621000277?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621000277?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:00:14Z","timestamp":1761501614000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001621000277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["S1525001621000277"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.01.027","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.01.027","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"}]}}