{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:46:41Z","timestamp":1780570001219,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Urological Research Institute, San Raffaele Hospital, Milan, Italy"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Nabiximols (Sativex<jats:sup><jats:bold>\u00ae<\/jats:bold><\/jats:sup>) is a cannabinoid\u2010based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>). The aim of the study was to investigate the effect of the administration of Nabiximols on blood transcriptome profile of patients with <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and to interpret it in the context of pathways and networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010genome expression profiling was performed in whole blood of 33 subjects with <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> at baseline and after 4 weeks of drug treatment. Patients were classified as responders (<jats:italic>n<\/jats:italic> = 19) and non\u2010responders (<jats:italic>n<\/jats:italic> = 14). Pathway and network analyses on genes modulated by the drug were performed, followed by <jats:italic>in vitro<\/jats:italic> stimulation of peripheral blood mononuclear cells with pro\u2010inflammatory agents to support the immunomodulatory properties of the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Individual effect size was modest; however, we observed a downregulation of several immune\u2010related pathways after 4 weeks of treatment, which was more pronounced when restricting analyses to responders. Interesting hub molecules functionally related to the immune system emerged from network analysis, including <jats:italic><jats:styled-content style=\"fixed-case\">NFKB<\/jats:styled-content>1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">FYN<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>14<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic>. The immunomodulatory properties of the drug were confirmed through <jats:italic>in vitro<\/jats:italic> assays in peripheral blood mononuclear cells collected from patients with <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings support the immunomodulatory activity of cannabinoids in patients with <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>. Further studies in more specific cell types are needed to refine these results.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13623","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T14:54:53Z","timestamp":1520866493000},"page":"934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-2550","authenticated-orcid":false,"given":"M.","family":"Sorosina","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders CNS Inflammatory Unit Institute of Experimental Neurology IRCCS San Raffaele Scientific Institute Milan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Clarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders CNS Inflammatory Unit Institute of Experimental Neurology IRCCS San Raffaele Scientific Institute Milan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ferr\u00e8","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders CNS Inflammatory Unit Institute of Experimental Neurology IRCCS San Raffaele Scientific Institute Milan"},{"name":"Department of Neurology IRCCS San Raffaele Scientific Institute Milan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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