{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:42:03Z","timestamp":1789004523546,"version":"build-2803163510"},"reference-count":39,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis Journal \u2013 Experimental, Translational and Clinical"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To recover normal functions, remyelination in multiple sclerosis is crucial. Although endogenous remyelination occurs, it is often insufficient, and finding molecules promoting repair of demyelinated lesions is needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare the remyelination potential of evobrutinib, an inhibitor of Bruton's tyrosine kinase and clemastine, an antagonist of M1 muscarinic acetylcholine receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Remyelination was investigated in lysolecithin demyelinated organotypic mouse cerebellar slices and a transgenic\n                      <jats:italic toggle=\"yes\">Xenopus<\/jats:italic>\n                      model of inducible-demyelination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Evobrutinib (100 nM) and clemastine (200 nM) potentiated remyelination of mouse cerebellar slices by a factor of 2.9 and 1.76, respectively. In conditionally demyelinated\n                      <jats:italic toggle=\"yes\">Xenopus<\/jats:italic>\n                      , evobrutinib and clemastine increased remyelination by a factor of 1.61 and 1.92, respectively. Evobrutinib targets Bruton's tyrosine kinase expressed by microglia, and we showed that the increase in number of myeloid cells following demyelination is due to an extravasation from nearby vessels of macrophages migrating toward the optic nerve. In contrast, clemastine is expected to antagonize muscarinic receptor 1 expressing cells of the oligodendroglial lineage. We investigated a possible synergistic effect on remyelination by adding simultaneously both molecules. In both experimental models tested no significative improvement on remyelination of co-treatment with evobrutinib plus clemastine was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>While evobrutinib increased 1.59 fold the number of microglia\/macrophages, in the presence of clemastine the number of innate immune cells was decreased by 0.39 fold, therefore counteracting the beneficial effect of microglia\/macrophages on remyelination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20552173251326913","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T17:14:18Z","timestamp":1742577258000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Positive effect of evobrutinib in CNS remyelination models and lack of synergy with clemastine\u2014A dose response study"],"prefix":"10.1177","volume":"11","author":[{"given":"E.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.S.","family":"Aigrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Fr\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Lepaulmier","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Stankoff","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9"},{"name":"Sorbonne Universit\u00e9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Boschert","sequence":"additional","affiliation":[{"name":"Ares Trading S.A. an affiliate of Merck Serono S.A., Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lubetzki","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9"},{"name":"Sorbonne Universit\u00e9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-9827","authenticated-orcid":false,"given":"B.","family":"Zalc","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0021-5198(19)43508-7","article-title":"Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay","volume":"43","author":"Kubo N","year":"1987","unstructured":"Kubo N, Shirakawa O, Kuno T, et al. 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