Authors: Lalive, Patrice H.; Neuhaus, Oliver¹; Benkhoucha, Mahdia²; Burger, Danielle³; Hohlfeld, Reinhard⁴; Zamvil, Scott S.⁵; Weber, Martin S.⁶

Source: CNS Drugs, Volume 25, Number 5, 1 May 2011 , pp. 401-414(14)

Publisher: Adis International

Abstract:

Glatiramer acetate is a synthetic, random copolymer widely used as a first-line agent for the treatment of relapsing-remitting multiple sclerosis (MS). While earlier studies primarily attributed its clinical effect to a shift in the cytokine secretion of CD4+ T helper (T_h) cells, growing evidence in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), suggests that glatiramer acetate treatment is associated with a broader immunomodulatory effect on cells of both the innate and adaptive immune system. To date, glatiramer acetate-mediated modulation of antigen-presenting cells (APC) such as monocytes and dendritic cells, CD4+ T_h cells, CD8+ T cells, Foxp3+ regulatory T cells and antibody production by plasma cells have been reported; in addition, most recent investigations indicate that glatiramer acetate treatment may also promote regulatory B-cell properties. Experimental evidence suggests that, among these diverse effects, a fostering interplay between anti-inflammatory T-cell populations and regulatory type II APC may be the central axis in glatiramer acetate-mediated immune modulation of CNS autoimmune disease. Besides altering inflammatory processes, glatiramer acetate could exert direct neuroprotective and/or neuroregenerative properties, which could be of relevance for the treatment of MS, but even more so for primarily neurodegenerative disorders, such as Alzheimer's or Parkinson's disease. In this review, we provide a comprehensive and critical overview of established and recent findings aiming to elucidate the complex mechanism of action of glatiramer acetate.

Keywords: Glatiramer-acetate, pharmacodynamics; Immunomodulators, pharmacodynamics; Multiple-sclerosis

Document Type: Research article

Affiliations: 1: 4 Department of Neurology, Kliniken Landkreis Sigmaringen, Sigmaringen, Germany 2: 3 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland 3: 5 Faculty of Medicine, Division of Immunology and Allergy, Hans Wilsdorf Laboratory, Geneva University Hospital and University of Geneva, Geneva, Switzerland 4: 6 Institute for Clinical Neuroimmunology, Ludwig-Maximilians University of Munich, Munich, Germany 5: 7 Department of Neurology, University of California, San Francisco, California, USA 6: 8 Department of Neurology, Technische Universität München, Munich, Germany

Publication date: 2011-05-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Lalive, Patrice H. ;  Neuhaus, Oliver ;  Benkhoucha, Mahdia ;  Burger, Danielle ;  Hohlfeld, Reinhard ;  Zamvil, Scott S. ;  Weber, Martin S.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers