{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:17:22Z","timestamp":1792412242397,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWO\u2010TBM 2021"],"award-info":[{"award-number":["FWO\u2010TBM 2021"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["T001121N"],"award-info":[{"award-number":["T001121N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Regenerative strategies in progressive multiple sclerosis (MS) pose a significant unmet need. Combining immunomodulatory treatment with remyelinating interventions to target the complex underlying pathogenesis appeals as the next frontier in MS therapeutic developments. Therefore, it is important to identify which disease\u2010modifying treatments (DMT) with proremyelinating properties are most promising for future use in combination treatments. This systematic review provides an overview of preclinical and clinical research on remyelination, focusing on the effects of currently available FDA and EMA\u2010approved DMT\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The search was conducted in accordance with the \u201cSynthesis without meta\u2010analysis\u201d (SWiM) reporting guideline. The protocol was registered at PROSPERO prior to the search.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty\u2010seven articles on preclinical research, three randomized controlled trials (RCTs), 29 non\u2010randomized clinical studies, and eight reviews were included. Preclinical research suggested neuroprotective properties of various DMT. However, convincing evidence of true remyelination, either by influencing oligodendrocyte lineage cells in cell cultures or histological analysis in\u00a0vivo, could only be found in studies investigating glatiramer acetate, teriflunomide, Fingolimod, Siponimod, Ponesimod, and alemtuzumab. Clinical trials using surrogate markers of myelin repair, such as advanced imaging and electrophysiological techniques, demonstrated promising results with glatiramer acetate, Fingolimod, Siponimod, natalizumab, alemtuzumab, and ocrelizumab. However, we found insufficient proof to claim that changes in these surrogate markers can be explained by remyelination alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Future proof\u2010of\u2010concept clinical trials investigating remyelinating agents in MS should consider combining outcome measures into composite endpoints. Furthermore, research efforts should be dedicated to novel biomarkers to assess repair mechanisms in MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70397","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:00:55Z","timestamp":1762858855000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved Disease\u2010Modifying Treatments for Multiple Sclerosis"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-807X","authenticated-orcid":false,"given":"Anna\u2010Victoria","family":"De Keersmaecker","sequence":"first","affiliation":[{"name":"Translational Sciences Research Group, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"},{"name":"Department of Neurology Antwerp University Hospital, University of Antwerp  Edegem Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"van Doninck","sequence":"additional","affiliation":[{"name":"Department Family Medicine and Population Health (FAMPOP), Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez","family":"Wens","sequence":"additional","affiliation":[{"name":"Repair\u2010Inducing Cognition Enhancers, Department of Neuroscience, Biomedical Research Institute \u2013 Faculty of Medicine and Life Sciences Universitair MS Centrum (UMSC)  Diepenbeek Belgium"},{"name":"Department of Psychiatry &amp; Neuropsychology, School for Mental Health and Neuroscience \u2013 Division Translational Neuroscience, Faculty of Health Medicine and Life Sciences Maastricht University  Maastrich the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousra","family":"El Ouaamari","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, VAXINFECTIO, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Popescu","sequence":"additional","affiliation":[{"name":"Immunology &amp; Infection (IMIN), Biomedical Research Institute (BIOMED) University Hasselt  Diepenbeek Belgium"},{"name":"Department of Neurology Noorderhart Maria Hospital  Pelt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Laureys","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences University of Ghent  Ghent Belgium"},{"name":"Department of Neurology Universital Hospital Ghent  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Cambron","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences University of Ghent  Ghent Belgium"},{"name":"Department of Neurology AZ Sint Jan  Bruges Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"D'Haeseleer","sequence":"additional","affiliation":[{"name":"Department Neuroprotection &amp; Neuromodulation (NEUR), Center for Neurosciences, Faculty of Medicine and Pharmacy Vrije Universiteit Brussel  Jette Belgium"},{"name":"Department of Neurology Universital Hospital Brussels  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lander","family":"Willem","sequence":"additional","affiliation":[{"name":"Department Family Medicine and Population Health (FAMPOP), Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"},{"name":"Centre for Health Economic Research and Modelling Infectious Diseases (CHERMID) University of Antwerp  Wilrijk Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Derdelinckx","sequence":"additional","affiliation":[{"name":"Department of Neurology Antwerp University Hospital, University of Antwerp  Edegem Belgium"},{"name":"Laboratory of Experimental Hematology, VAXINFECTIO, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Reynders","sequence":"additional","affiliation":[{"name":"Translational Sciences Research Group, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"},{"name":"Department of Neurology Antwerp University Hospital, University of Antwerp  Edegem Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Willekens","sequence":"additional","affiliation":[{"name":"Translational Sciences Research Group, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"},{"name":"Department of Neurology Antwerp University Hospital, University of Antwerp  Edegem Belgium"},{"name":"Laboratory of Experimental Hematology, VAXINFECTIO, Faculty of Medicine and Health Sciences University of Antwerp  Wilrijk Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1401483"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520970841"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000000560"},{"key":"e_1_2_8_5_1","unstructured":"G.Schrimpf \u201cMerck KGaA Darmstadt Germany Provides Update on Phase III Results for Evobrutinib in Relapsing Multiple Sclerosis\u201d."},{"key":"e_1_2_8_6_1","unstructured":"H.Trees \u201cRoche's Fenebrutinib Demonstrated Near\u2010Complete Suppression of Disease Activity and Disability Progression for Up to 48\u2009Weeks in Patients With Relapsing Multiple Sclerosis\u201d."},{"key":"e_1_2_8_7_1","unstructured":"S.Guendoul \u201cTolebrutinib Demonstrated a 31% Delay in Time to Onset of Confirmed Disability Progression in Non\u2010Relapsing Secondary Progressive Multiple Sclerosis Phase 3 Study\u201d."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(24)00328\u20104"},{"key":"e_1_2_8_9_1","unstructured":"H.Trees \u201cRoche's Fenebrutinib Maintains Near\u2010Complete Suppression of Disease Activity and Disability Progression for Up to Two Years in People With Relapsing Multiple Sclerosis \u201dSecondary Roche's Fenebrutinib Maintains Near\u2010Complete Suppression of Disease Activity and Disability Progression for Up To Two Years in People With Relapsing Multiple Sclerosis 2025 https:\/\/www.roche.com\/media\/releases\/med\u2010cor\u20102025\u201005\u201030."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415988"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(22)00289\u20107"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac111"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/con.0000000000000727"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24655"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001366\u20109"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010025\u201001927\u20100"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800763-1.00013-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2005.11.007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2014.969241"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(20)30140\u2010x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106230"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517721355"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109072\u20106_14"},{"key":"e_1_2_8_24_1","unstructured":"J. H.JohnsonandY.Al Khalili \u201cMyelin. Secondary Myelin \u201d(2023) https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK541009\/."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101304"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007754"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010019\u201009421\u2010x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13020357"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac207"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458508095731"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjno\u20102023\u2010000560"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000007099"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac436"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u2010981\u201032\u20109636\u20107_15"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27102"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103166"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115877"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3469"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00047"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.05.006"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113574"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2025.2510405"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2021.100901"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102015"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010023\u201001402\u20103"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12154"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.94.15_supplement.2868"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010023\u201001326\u20107"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.98.18_supplement.1280"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2023.107333"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23416"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T07:01:35Z","timestamp":1764313295000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.70397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/ene.70397"],"URL":"https:\/\/doi.org\/10.1111\/ene.70397","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-04-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70397"}}