{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:15:21Z","timestamp":1782306921416,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Samsung Medical Center","award":["GFO2170061"],"award-info":[{"award-number":["GFO2170061"]}]},{"name":"AnGes MG, Inc","award":["PHX0143471"],"award-info":[{"award-number":["PHX0143471"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis II (MPS II) is caused by a deficiency of iduronate\u20102\u2010sulfatase that results in accumulation of glycosaminoglycans (GAG), including heparan sulfate (HS), which is considered to contribute to neuropathology. We examined the efficacy of intracerebroventricular (ICV) enzyme replacement therapy (ERT) of idursulfase\u2010beta (IDS\u2010\u03b2) and evaluated the usefulness of HS as a biomarker for neuropathology in MPS II mice. We first examined the efficacy of three different doses (3, 10, and 30 \u03bcg) of single ICV injections of IDS\u2010\u03b2 in MPS II mice. After the single\u2010injection study, its long\u2010term efficacy was elucidated with 30 \u03bcg of IDS\u2010\u03b2 ICV injections repeated every 4 weeks for 24 weeks. The efficacy was assessed by the HS content in the cerebrospinal fluid (CSF) and the brain of the animals along with histologic examinations and behavioral tests. In the single\u2010injection study, the 30 \u03bcg of IDS\u2010\u03b2 ICV injection showed significant reductions of HS content in brain and CSF that were maintained for 28 days. Furthermore, HS content in CSF was significantly correlated with HS content in brain. In the long\u2010term repeated\u2010injection study, the HS content in the brain and CSF was also significantly reduced and correlated. The histologic examinations showed a reduction in lysosomal storage. A significant improvement in memory\/learning function was observed in open\u2010field and fear\u2010conditioning tests. ICV ERT with 30 \u03bcg of IDS\u2010\u03b2 produced significant improvements in biochemical, histological, and functional parameters in MPS II mice. Furthermore, we demonstrate for the first time that the HS in the CSF had significant positive correlation with brain tissue HS and GAG levels, suggesting HS in CSF as a useful clinical biomarker for neuropathology.<\/jats:p>","DOI":"10.1007\/s10545-018-0221-0","type":"journal-article","created":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T13:42:29Z","timestamp":1530798149000},"page":"1235-1246","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The efficacy of intracerebroventricular idursulfase\u2010beta enzyme replacement therapy in mucopolysaccharidosis II murine model: heparan sulfate in cerebrospinal fluid as a clinical biomarker of neuropathology"],"prefix":"10.1002","volume":"41","author":[{"given":"Young Bae","family":"Sohn","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Ajou University Hospital Ajou University School of Medicine Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah\u2010Ra","family":"Ko","sequence":"additional","affiliation":[{"name":"Research Institute for Future Medicine Samsung Biomedical Research Center Seoul Republic of Korea"},{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine 81, Irwon\u2010ro, Gangnam\u2010gu Seoul 06351 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010ran","family":"Seong","sequence":"additional","affiliation":[{"name":"Research Institute for Future Medicine Samsung Biomedical Research Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute for Future Medicine Samsung Biomedical Research Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Ra","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute for Future Medicine Samsung Biomedical Research Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Yoon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine 81, Irwon\u2010ro, Gangnam\u2010gu Seoul 06351 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Genomics, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea"},{"name":"Department of Health Sciences and Technology Sungkyunkwan University SAIHST Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"AnGes, Inc. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"AnGes, Inc. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomichi","family":"Kosuga","sequence":"additional","affiliation":[{"name":"Center for Lysosomal Storage Diseases National Center for Child Health and Development 2\u201010\u20101, Ohkura, Setagaya\u2010ku Tokyo 157\u20108535 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyun","family":"Seo","sequence":"additional","affiliation":[{"name":"Center for Lysosomal Storage Diseases National Center for Child Health and Development 2\u201010\u20101, Ohkura, Setagaya\u2010ku Tokyo 157\u20108535 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torayuki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Center for Lysosomal Storage Diseases National Center for Child Health and Development 2\u201010\u20101, Ohkura, Setagaya\u2010ku Tokyo 157\u20108535 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Kyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine 81, Irwon\u2010ro, Gangnam\u2010gu Seoul 06351 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.09.013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.10.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.7.2134"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992289803700302"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.09.012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030341"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-014-1461-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-015-9684-y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9535-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0641-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2238"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1957.tb01354.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0325-3"},{"issue":"1","key":"e_1_2_7_15_1","first-page":"S118","article-title":"Delivery of recombinant proteins via the cerebrospinal fluid as a therapy option for neurodegenerative lysosomal storage diseases","volume":"47","author":"Hemsley KM","year":"2009","journal-title":"Int J Clin Pharmacol Ther"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.05.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-11-26"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-010-0083-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.07.003"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32781"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.897"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.36"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.011"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq420"},{"key":"e_1_2_7_25_1","first-page":"e52434","article-title":"Use of the Open Field Maze to measure locomotor and anxiety\u2010like behavior in mice","volume":"96","author":"Seibenhener ML","year":"2015","journal-title":"J Vis Exp"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34371"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035787"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0635-4"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1007%2Fs10545-018-0221-0","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10545-018-0221-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-018-0221-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-018-0221-0","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-018-0221-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:08:26Z","timestamp":1694657306000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-018-0221-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,5]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1007\/s10545-018-0221-0"],"URL":"https:\/\/doi.org\/10.1007\/s10545-018-0221-0","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,5]]}}}