{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:10:05Z","timestamp":1790820605304,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Enzyme replacement therapy (ERT) improves somatic manifestations in mucopolysaccharidoses (MPS). However, because intravenously administered enzymes cannot cross the blood\u2013brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT in order to achieve CNS effects, but the burdens on patients are inimical to long-term administrations. However, since pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in a mouse model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT that is effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the previously obtained preclinical and clinical evidence related to the use of this drug, presents latest data, and discusses the preclinical, translational, and clinical challenges of evaluating, ameliorating, and preventing neurodegeneration in patients with MPS-II.<\/jats:p>","DOI":"10.3390\/ijms222010938","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: An Integrated Analysis of Preclinical and Clinical Data"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-3686","authenticated-orcid":false,"given":"Roberto","family":"Giugliani","sequence":"first","affiliation":[{"name":"Department of Genetics, Hospital de Cl\u00ednicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Martins","sequence":"additional","affiliation":[{"name":"Reference Center in Inborn Errors of Metabolism, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torayuki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Center for Lysosomal Storage Diseases, National Centre for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikatsu","family":"Eto","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Centre & Asian Lysosome Storage Disorder Centre, Institute of Neurological Disorders, Kanagawa 215-0026, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-6709","authenticated-orcid":false,"given":"Norio","family":"Sakai","sequence":"additional","affiliation":[{"name":"Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kumamoto University Graduate School of Medical Science, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Morimoto","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohtaro","family":"Minami","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyoshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Ikeda","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairei","family":"So","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Tanizawa","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sonoda","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Schmidt","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-8643","authenticated-orcid":false,"given":"Yuji","family":"Sato","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals, Hyogo 659-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"ref_1","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. 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