{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:40:34Z","timestamp":1783698034044,"version":"3.55.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian MPS Society"},{"name":"A Cure for Robert, Inc."},{"name":"The Carol Ann Foundation"},{"name":"Angelo R. Cali & Mary V. Cali Family Foundation, Inc."},{"name":"The Vain and Harry Fish Foundation, Inc."},{"DOI":"10.13039\/100018298","name":"The Bennett Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018298","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004075","name":"Jacob Randall Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004075","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"Institutional Development Award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD102545-01A1"],"award-info":[{"award-number":["1R01HD102545-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013394","name":"REGENXBIO Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013394","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, which leads to the accumulation of chondroitin-6-sulfate and keratan sulfate, primarily in cartilage and its extracellular matrix, resulting in a direct impact on cartilage and bone development, as well as subsequent systemic skeletal dysplasia. ERT and HSCT are current treatment options, but they have a limited effect on bone lesions. In this article, we investigated liver-specific AAV8 vectors with a thyroxine-binding globulin promoter in the MPS IVA murine model to evaluate the long-term (24 weeks in males and 48 weeks in females) effects of gene therapy on biochemical markers and bone pathology. Both treated groups showed GALNS enzyme activity at supraphysiological levels in plasma and in various tissues, including the liver, heart, spleen, and bone. Keratan sulfate in both groups was normalized in plasma, liver, and bone (male mice). Pathological analyses revealed a decrease in vacuolated cells in the heart muscle and valves and improvement in bone pathology in treated male mice. However, the therapeutic impact was less pronounced in treated female mice. Overall, male mice indicated a substantial improvement in biochemical parameters and pathology compared to female mice.<\/jats:p>","DOI":"10.3390\/cimb47110900","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T03:44:39Z","timestamp":1761795879000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long-Term Liver-Targeted AAV8 Gene Therapy for Mucopolysaccharidosis IVA"],"prefix":"10.3390","volume":"47","author":[{"given":"Shaukat A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-2716","authenticated-orcid":false,"given":"Eliana","family":"Benincore-Florez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FNU","family":"Nidhi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-1341","authenticated-orcid":false,"given":"Jose Victor","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Hospital Cl\u00ednico Universitario de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dione A.","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Shimane University, Izumo 693-8501, Japan"},{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0006-291X(74)91022-5","article-title":"Morquio\u2019s syndrome: Deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase","volume":"61","author":"Matalon","year":"1974","journal-title":"Biochem. 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