{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:01:29Z","timestamp":1784682089387,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease characterized by hepatosplenomegaly, pulmonary dysfunction, dyslipidemia, and growth deficits. Olipudase alfa (recombinant\u2010human ASM) is the only treatment for non\u2010central\u2010nervous\u2010system ASMD manifestations in children and adults. An open\u2010label long\u2010term study followed 4 to 8\u2009years of olipudase alfa treatment in 20 children and adolescents with ASMD (baseline age (years) 1.5\u201317.5). At final assessments, splenomegaly and hepatomegaly were reduced relative to baseline (mean percent decrease in spleen and liver volumes 78%\u2009\u00b1\u20091.2% and 59.8%\u2009\u00b1\u20091.5%, respectively). Baseline splenomegaly was severe (spleen volume\u2009&gt;\u200915 MN [multiples of normal]) or moderate (5\u201315 MN) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912 and\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098, respectively) versus mild\/absent (&lt;\u20095 MN) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) or moderate (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) at final assessment. Baseline hepatomegaly was severe (liver volume &gt;\u20092.5 MN) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) or moderate (1.25\u20132.5 MN) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) versus mild\/absent (&lt;\u20091.25 MN) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919) or moderate (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091) at final assessment. Among nine individuals able to perform assessments, diffusing capacity of the lung for carbon monoxide (DL\n                    <jats:sub>CO<\/jats:sub>\n                    ) impairment was severe (&lt;\u200940%) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), moderate (40%\u201360%) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), or mild (60%\u201380%) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) at baseline versus absent (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), mild (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) or moderate (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091) at final assessment. Mean percent increase in DL\n                    <jats:sub>CO<\/jats:sub>\n                    was 53.7%\u2009\u00b1\u20096.5%. At baseline, 10\/20 children had clinical short stature (height\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010scores \u2264\u2009\u2212\u20092) at baseline versus 0\/20 at the final assessment. Atherogenic lipid profiles and liver function tests normalized within 2\u2009years and remained stable. Adverse events were mostly mild or moderate, with 4 individuals experiencing 7 serious adverse events, all recovered\/resolved. Interpretation: Enzyme replacement therapy with olipudase alfa in children and adolescents with chronic ASMD was well\u2010tolerated with clinically meaningful improvements in multiple disease parameters.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    NCT02004704.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70086","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:16:03Z","timestamp":1757668563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency"],"prefix":"10.1002","volume":"48","author":[{"given":"Maurizio","family":"Scarpa","sequence":"first","affiliation":[{"name":"Regional Coordinating Centre for Rare Diseases University Hospital of Udine  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Medical Genetics Service HCPA, Department of Genetics UFRGS, INAGEMP, DASA Genomica and Casa dos Raros  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Genomic Medicine Manchester University National Health Service Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mengel","sequence":"additional","affiliation":[{"name":"SphinCS GmbH, Institute of Clinical Science for Lysosomal Storage Disorders  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Guffon","sequence":"additional","affiliation":[{"name":"Reference Centre of Inherited Metabolic Disease in Femme M\u00e8re Enfant Hospital, Hospices Civils of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Witters","sequence":"additional","affiliation":[{"name":"Center for Metabolic Diseases, Department of Paediatrics University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Global Safety, Sanofi, Bridgewater  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinical Development, Sanofi  Paris 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