{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:29:07Z","timestamp":1770276547757,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the longitudinal correlations between sulfatide\/lysosulfatide levels and central and peripheral nervous system function in children with metachromatic leukodystrophy (MLD) and to explore the impact of intravenous recombinant human arylsulfatase A (rhASA) treatment on myelin turnover.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A Phase 1\/2 study of intravenous rhASA investigated cerebrospinal fluid (CSF) and sural nerve sulfatide levels, 88\u2010item Gross Motor Function Measure (GMFM\u201088) total score, sensory and motor nerve conduction, brain <jats:italic>N<\/jats:italic>\u2010acetylaspartate (NAA) levels, and sural nerve histology in 13 children with MLD. Myelinated and unmyelinated nerves from an untreated MLD mouse model were also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSF sulfatide levels correlated with neither <jats:italic>Z<\/jats:italic>\u2010scores for GMFM\u201088 nor brain NAA levels; however, CSF sulfatide levels correlated negatively with <jats:italic>Z<\/jats:italic>\u2010scores of nerve conduction parameters, number of large (\u22657\u2009\u03bcm) myelinated fibers, and myelin\/fiber diameter slope, and positively with nerve g\u2010ratios and cortical latencies of somatosensory\u2010evoked potentials. Quantity of endoneural litter positively correlated with sural nerve sulfatide\/lysosulfatide levels. CSF sulfatide levels decreased with continuous high\u2010dose treatment; this change correlated with improved nerve conduction. At 26\u2009weeks after treatment, nerve g\u2010ratio decreased by 2%, and inclusion bodies per Schwann cell unit increased by 55%. In mice, abnormal sulfatide storage was observed in non\u2010myelinating Schwann cells in Remak bundles of sciatic nerves but not in unmyelinated urethral nerves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Lower sulfatide levels in the CSF and peripheral nerves correlate with better peripheral nerve function in children with MLD; intravenous rhASA treatment may reduce CSF sulfatide levels and enhance sulfatide\/lysosulfatide processing and remyelination in peripheral nerves.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51954","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T08:35:15Z","timestamp":1703579715000},"page":"328-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy"],"prefix":"10.1002","volume":"11","author":[{"given":"Mohamed H.","family":"Farah","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine \u00ed","family":"Dali","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology University Children's Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Neuroscience University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A. 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