{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:56:37Z","timestamp":1789764997013,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","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":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Natalizumab (NTZ) is a highly effective therapy for multiple sclerosis (MS); however, its use is limited by the risk of a rare potentially severe opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). Alternative dosing strategies are evaluated to reduce PML risk while still maintaining efficacy, which include extending the dosing interval (EID) or a lesser\u2010known annual dosing gap (aGAP), which is the focus of this prospective observational single\u2010site cohort study. We evaluated whether aGAP affects the efficacy of NTZ, which biomarkers could be useful for a personalized dosing strategy, and potential cellular mechanisms that might contribute to reducing the risk of PML during aGAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical assessments, quantifications of NTZ, neurofilament light chain (NfL), and soluble vascular cell adhesion molecule\u20101 (sVCAM\u20101) were performed for ten study participants of a clinical trial (NCT04048577); CSF single\u2010cell RNA\u2010sequencing data from nine participants (15 samples) were analyzed together with 48 healthy and 35 MS controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Although NTZ serum levels were decreased below EID levels and sVCAM\u20101 levels were increased, aGAP was not associated with MS activity as measured by EDSS and MRI. After aGAP, while CSF cell counts remained stable, the CSF immune cell composition changed and NfL values were increased 3 months post gap. CSF proportions of CD4, CD8, and natural killer cell subsets increased towards levels of untreated MS patients, while B\u2010cell proportions remained unchanged.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The differential CSF composition associated with sVCAM\u20101 serum level changes suggests that selective immune cell trafficking may occur during aGAP, potentially contributing to PML prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70207","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T06:55:36Z","timestamp":1758696936000},"page":"85-96","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Annual 12\u2010Week Dosing Gap of Natalizumab: Clinical Efficacy, Blood Biomarkers, and\n                    <scp>CSF<\/scp>\n                    Cell Composition"],"prefix":"10.1002","volume":"13","author":[{"given":"Regina","family":"Berkovich","sequence":"first","affiliation":[{"name":"Berkovich MS Center and Research Institute  West Hollywood California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3717-5176","authenticated-orcid":false,"given":"Tilman","family":"Schneider\u2010Hohendorf","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-1328","authenticated-orcid":false,"given":"Eric","family":"Baetscher","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Center Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan L.","family":"Riddle","sequence":"additional","affiliation":[{"name":"Biogen  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