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Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis

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dc.contributor.author Correale, Jorge
dc.contributor.author Halfon, Mario Javier
dc.contributor.author Jack, Dominic
dc.contributor.author Rubstein, Adrián
dc.contributor.author Villa, Andrés
dc.date.accessioned 2021-10-20T14:51:53Z
dc.date.available 2021-10-20T14:51:53Z
dc.date.issued 2021-09-14
dc.identifier.citation Correale J, Halfon MJ, Jack D, Rubstein A, Villa A. Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis. Mult Scler Relat Disord. 2021 Sep 14;56:103264. doi: 10.1016/j.msard.2021.103264 es_ES
dc.identifier.uri https://doi.org/10.1016/j.msard.2021.103264
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/609
dc.description.abstract With the recent approval of cladribine tablets, siponimod and ozanimod, there has been a renewed interest into the extent to which these current generation disease-modifying therapies (DMTs) are able to cross into the central nervous system (CNS), and how this penetration of the blood-brain barrier (BBB) may influence their ability to treat multiple sclerosis (MS). The integrity of the CNS is maintained by the BBB, blood-cerebrospinal fluid barrier, and the arachnoid barrier, which all play an important role in preserving the immunological environment and homeostasis within the CNS. The integrity of the BBB decreases during the course of MS, with a putative temporal relationship to disease worsening. Furthermore, it is currently considered that progression of the disease is mediated mainly by resident cells of the CNS. The existing literature provides evidence to show that some of the current generation DMTs for MS are able to penetrate the CNS and potentially exert direct effects on CNS-resident cells, in particular the CNS-penetrating prodrugs cladribine and fingolimod, and other sphingosine-1 phosphate receptor modulators; siponimod and ozanimod. Other current generation DMTs appear to be restricted to the periphery due to their high molecular weight or physicochemical properties. As more effective brain penetrant therapies are developed for the treatment of MS, there is a need to understand whether the potential for direct effects within the CNS are of significance, and whether this brings additional benefits over and above treatment effects mediated in the periphery. In turn, this will require an improved understanding of the structure and function of the BBB, the role it plays in MS and subsequent treatments. This narrative review summarizes the data supporting the biological plausibility of a potential benefit from therapeutic molecules entering the CNS, and discusses the potential significance in the current and future treatment of MS. es_ES
dc.language.iso eng es_ES
dc.publisher Elsevier es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Multiple Sclerosis es_ES
dc.subject Esclerosis Múltiple es_ES
dc.subject Blood-Brain Barrier es_ES
dc.subject Barrera Hematoencefálica es_ES
dc.subject Central Nervous System es_ES
dc.subject Sistema Nervioso Central es_ES
dc.subject Cerebrospinal Fluid es_ES
dc.subject Líquido Cefalorraquídeo es_ES
dc.title Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.
dc.description.fil Fil: Halfon, Mario Javier. Hospital Británico de Buenos Aires; Argentina.
dc.description.fil Fil: Jack, Dominic. Merck Serono Ltd; Reino Unido.
dc.description.fil Fil: Rubstein, Adrián. Merck S.A.; Argentina.
dc.description.fil Fil: Villa, Andrés. Hospital Ramos Mejía; Argentina.
dc.relation.ispartofVOLUME 56
dc.relation.ispartofPAGINATION 103264
dc.relation.ispartofCOUNTRY Países Bajos
dc.relation.ispartofCITY Amsterdam
dc.relation.ispartofTITLE Multiple sclerosis and related disorders
dc.relation.ispartofISSN 2211-0356
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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