Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action.
Glatiramer acetate is a synthetic random copolymer approved for the immunomodulatory therapy of relapsing-type multiple sclerosis (MS). Previous work has focused on the effects of this drug on T cells, especially the glatiramer-acetate-induced shift of the cytokine profile towards those characteristic of T-helper-2 (Th2) cells. Glatiramer acetate was thought to bring about this Th2 shift by acting like an altered peptide ligand but more recent work has shown that the drug notably affects the properties of antigen-presenting cells, such as monocytes and dendritic cells. These new observations might offer an explanation for the previously observed Th2 shift. In this review, we focus on these new findings. We address several controversial issues, including the possible neurotrophic effects of glatiramer acetate, the potential role of neutralising antibodies to the drug, and attempts to develop biomarkers of the treatment response. Finally, we will think about how a better understanding of glatiramer acetate might help the development of new immunomodulatory agents for MS.
Farina
Cinthia
C
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Weber
Martin S
MS
Meinl
Edgar
E
Wekerle
Hartmut
H
Hohlfeld
Reinhard
R
D000906:Antibodies; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000906:Antibodies; D015415:Biomarkers; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate