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New Directions in Multiple Sclerosis Therapy: Matching Therapy with Pathogenesis

Published online by Cambridge University Press:  02 December 2014

Jack Antel
Jack Antel*
Affiliation:
Neuroimmunnology Unit, Montreal Neurologic Institute, Montreal, Quebec, Canada
*
Neuroimmunnology Unit, Montreal Neurologic Institute, 3801 University St., Room 111, Montreal, Quebec, H3A2B4, Canada.
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Abstract:

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All currently approved therapies for multiple sclerosis (MS) modulate systemic immune components prior to their entry into the central nervous system (CNS). Available data indicate they lack impact on the progressive phases of disease; the more potent systemic immune-directed agents predispose to development of infectious or neoplastic disorders. Development of new agents that enhance disease stage related efficacy and limit systemic toxicity will need to consider the underlying mechanisms related to each phase of the clinical disorder, namely relapses, remission, and progression. This report focuses on disease related mechanisms ongoing within the CNS that contribute to the different phases of MS and how these may serve as potential therapeutic targets. Such mechanisms include CNS compartment specific immunologic properties especially as related to the innate immune system and neural cell-related properties that are determinants of the extent of actual tissue injury and repair (or lack thereof).

Résumé:

RÉSUMÉ:

Tous les médicaments approuvés actuellement pour le traitement de la sclérose en plaques (SP) modulent des composantes immunitaires systémiques avant leur entrée dans le système nerveux central (SNC). Selon certaines données, ils n'auraient pas d'impact sur les phases progressives de la maladie. Les agents systémiques les plus puissants dirigés contre la réponse immunitaire prédisposent à l'apparition de maladies infectieuses ou néoplasiques. Le développement de nouveaux agents thérapeutiques qui rehaussent l'efficacité en relation avec le stade de la maladie et limitent la toxicité systémique devra tenir compte des mécanismes sous-jacents à chaque phase de la maladie clinique dont les récidives, les rémissions et la progression. Cet article met l'emphase sur les mécanismes évolutifs reliés à la maladie dans le SNC, qui contribuent aux différentes phases de la SP, et comment ces mécanismes pourraient servir de cibles thérapeutiques potentielles. Ces mécanismes incluent les propriétés immunologiques spécifiques de chaque compartiment du SNC surtout en relation avec le système immunitaire inné et avec les propriétés des cellules nerveuses qui sont des déterminants de l'étendue de la lesion tissulaire et de sa réparation (ou de l'absence de réparation).

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , supplement S2 , September 2010 , pp. S42 - S48
Copyright
Copyright © Canadian Neurological Sciences Federation 2010

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