{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:23:44Z","timestamp":1791685424484,"version":"4.3.4"},"reference-count":96,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oryzon Genomics, S.A.","award":["RTC-2016-4955-1"],"award-info":[{"award-number":["RTC-2016-4955-1"]}]},{"name":"Oryzon Genomics, S.A.","award":["CIIP-20152001\/E!9683"],"award-info":[{"award-number":["CIIP-20152001\/E!9683"]}]},{"name":"Oryzon Genomics, S.A.","award":["IDI-20180117"],"award-info":[{"award-number":["IDI-20180117"]}]},{"name":"RETOS","award":["RTC-2016-4955-1"],"award-info":[{"award-number":["RTC-2016-4955-1"]}]},{"name":"RETOS","award":["CIIP-20152001\/E!9683"],"award-info":[{"award-number":["CIIP-20152001\/E!9683"]}]},{"name":"RETOS","award":["IDI-20180117"],"award-info":[{"award-number":["IDI-20180117"]}]},{"name":"EUROSTAR II: EMTherapy","award":["RTC-2016-4955-1"],"award-info":[{"award-number":["RTC-2016-4955-1"]}]},{"name":"EUROSTAR II: EMTherapy","award":["CIIP-20152001\/E!9683"],"award-info":[{"award-number":["CIIP-20152001\/E!9683"]}]},{"name":"EUROSTAR II: EMTherapy","award":["IDI-20180117"],"award-info":[{"award-number":["IDI-20180117"]}]},{"name":"CDTI: EDOTEM","award":["RTC-2016-4955-1"],"award-info":[{"award-number":["RTC-2016-4955-1"]}]},{"name":"CDTI: EDOTEM","award":["CIIP-20152001\/E!9683"],"award-info":[{"award-number":["CIIP-20152001\/E!9683"]}]},{"name":"CDTI: EDOTEM","award":["IDI-20180117"],"award-info":[{"award-number":["IDI-20180117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A forms a part of protein complexes that regulate the expression of genes involved in the onset and progression of diseases such as cancer, central nervous system (CNS) disorders, viral infections, and others. Vafidemstat (ORY-2001) is a clinical stage inhibitor of KDM1A in development for the treatment of neurodegenerative and psychiatric diseases. However, the role of ORY-2001 targeting KDM1A in neuroinflammation remains to be explored. Here, we investigated the effect of ORY-2001 on immune-mediated and virus-induced encephalomyelitis, two experimental models of multiple sclerosis and neuronal damage. Oral administration of ORY-2001 ameliorated clinical signs, reduced lymphocyte egress and infiltration of immune cells into the spinal cord, and prevented demyelination. Interestingly, ORY-2001 was more effective and\/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the inflammatory gene expression signature characteristic ofEAE in the CNS of mice more potently. In addition, ORY-2001 induced gene expression changes concordant with a potential neuroprotective function in the brain and spinal cord and reduced neuronal glutamate excitotoxicity-derived damage in explants. These results pointed to ORY-2001 as a promising CNS epigenetic drug able to target neuroinflammatory and neurodegenerative diseases and provided preclinical support for the subsequent design of early-stage clinical trials.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071420","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:41:10Z","timestamp":1657100470000},"page":"1420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A\/RCOR1\/HDAC Epigenetic Axis in Multiple Sclerosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Fernando","family":"Cavalcanti","sequence":"first","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-9020","authenticated-orcid":false,"given":"Elena","family":"Gonzalez-Rey","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez-Neyra, IPBLN-CSIC, PTS-Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-5982","authenticated-orcid":false,"given":"Mario","family":"Delgado","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez-Neyra, IPBLN-CSIC, PTS-Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara P.","family":"Falo","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez-Neyra, IPBLN-CSIC, PTS-Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-2316","authenticated-orcid":false,"given":"Leyre","family":"Mestre","sequence":"additional","affiliation":[{"name":"Department of Functional and Systems Neurobiology, Cajal Institute (CSIC), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Guaza","sequence":"additional","affiliation":[{"name":"Department of Functional and Systems Neurobiology, Cajal Institute (CSIC), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"O\u2019Valle","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, IBIMER and IBS-Granada, Granada University, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele M. P.","family":"Lufino","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Xaus","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mascar\u00f3","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Lunardi","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Sacilotto","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Dessanti","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1186-4918","authenticated-orcid":false,"given":"David","family":"Rotllant","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-902X","authenticated-orcid":false,"given":"Xavier","family":"Navarro","sequence":"additional","affiliation":[{"name":"Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, and Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Herrando-Grabulosa","sequence":"additional","affiliation":[{"name":"Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, and Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-2514","authenticated-orcid":false,"given":"Carlos","family":"Buesa","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-6867","authenticated-orcid":false,"given":"Tamara","family":"Maes","sequence":"additional","affiliation":[{"name":"Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornell\u00e0 de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.cell.2004.12.012","article-title":"Histone demethylation mediated by the nuclear amine oxidase homolog LSD1","volume":"119","author":"Shi","year":"2004","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nature04021","article-title":"An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation","volume":"437","author":"Lee","year":"2005","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature04020","article-title":"LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription","volume":"437","author":"Metzger","year":"2005","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1021\/ja909996p","article-title":"Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitors","volume":"132","author":"Culhane","year":"2010","journal-title":"J. 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