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CNS Drugs

, Volume 25, Issue 5, pp 401–414 | Cite as

Glatiramer Acetate in the Treatment of Multiple Sclerosis

Emerging Concepts Regarding its Mechanism of Action
  • Patrice H. Lalive
  • Oliver Neuhaus
  • Mahdia Benkhoucha
  • Danielle Burger
  • Reinhard Hohlfeld
  • Scott S. Zamvil
  • Martin S. WeberEmail author
Review Article

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 (Th) 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+ Th 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

Multiple Sclerosis Amyotrophic Lateral Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Antigen Present Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. P.H.L. is supported by grants from the Swiss National Foundation (♯310000-132705), the Swiss Multiple Sclerosis Society and the Alliance SEP association. D.B. is supported by the Swiss Multiple Sclerosis Society and the Hans Wilsdorf Foundation. R.H. received personal compensation for activities such as advisory boards, consultancy fees from TEVA/Sanofi-Aventis, Bayer/Schering, Merck-Serono, Biogen-Idec and Novartis. R.H. received grant support from Deutsche Forschungsgemeinschaft (DFG), BMBF-KKNMS, TEVA, Bayer/Schering, Merck-Serono, Biogen-Idec and Novartis. S.S.Z. is supported by grants from the National Institute of Health (RO1 AI073737, RO1 AI059709 and RO1 NS063008), the National Multiple Sclerosis Society (NMSS; RG 3622 and 3913), Dana Foundation, Guthy Jackson Charitable Foundation and the Maisin Foundation. M.S.W. received grant support from the NMSS (RG 445A1/T), TEVA, the Else Kröner Fresenius Stiftung (A69/2010), the Kommission für Klinische Forschung (KKF) of the Technische Universität München and the DFG (WE 3547/4−1). The other authors have no conflicts of interest to declare.

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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Patrice H. Lalive
    • 1
    • 2
    • 3
  • Oliver Neuhaus
    • 4
  • Mahdia Benkhoucha
    • 3
  • Danielle Burger
    • 5
  • Reinhard Hohlfeld
    • 6
  • Scott S. Zamvil
    • 7
  • Martin S. Weber
    • 8
    Email author
  1. 1.Department of Neurosciences, Division of NeurologyGeneva University Hospital and University of GenevaGenevaSwitzerland
  2. 2.Department of Genetics and Laboratory Medicine, Division of Laboratory MedicineGeneva University Hospital and University of GenevaGenevaSwitzerland
  3. 3.Department of Pathology and Immunology, Faculty of MedicineUniversity of GenevaGenevaSwitzerland
  4. 4.Department of NeurologyKliniken Landkreis SigmaringenSigmaringenGermany
  5. 5.Faculty of Medicine, Division of Immunology and Allergy, Hans Wilsdorf LaboratoryGeneva University Hospital and University of GenevaGenevaSwitzerland
  6. 6.Institute for Clinical NeuroimmunologyLudwig-Maximilians University of MunichMunichGermany
  7. 7.Department of NeurologyUniversity of CaliforniaSan FranciscoUSA
  8. 8.Department of NeurologyTechnische Universität MünchenMunichGermany

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