title: Gene expression analysis reveals functional pathways of glatiramer acetate activation.
abstract: BACKGROUND
  Glatiramer acetate (GA, Copaxone®), a mixture of polymers comprising four amino acids, is approved for treatment of relapsing-remitting multiple sclerosis and clinically isolated syndrome. GA mediates its activity by induction of GA-specific T cells that shift the T cell balance from a dominant proinflammatory phenotype (Th1/Th17) to an anti-inflammatory phenotype (Th2/Treg).
  
  
  OBJECTIVE
  To characterize the functional pathways by which GA acts on immune cells, the authors conducted gene expression profiling using glatiramoid-stimulated splenocytes.
  
  
  METHODS
  Mice were immunized with GA and harvested splenocytes were reactivated ex vivo with GA or a purported generic GA. Gene expression profiles and functional pathways were evaluated in reactivated splenocytes.
  
  
  RESULTS
  Overall, 1,474 genes were significantly upregulated or downregulated by GA. The main functional pathways induced by GA were: increased proliferation and activation of immune cells including T and B lymphocytes, stimulation of antigen presenting cells and differentiation of effector T lymphocytes. T-helper cell differentiation was the most significant canonical pathway associated with gene transcripts altered by GA. These expression patterns were not observed when splenocytes were activated with generic GA.
  
  
  CONCLUSIONS
  GA-induced functional pathways coincide with known mechanisms of GA activity in MS patients and further support the unique therapeutic effect of this drug.
authors.affiliation: Teva Pharmaceutical Industries, P.O. Box 8077, Netanya 42504, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bakshi
authors.forename: Vered
authors.initials: V
authors.lastname: Chalifa-Caspi
authors.forename: Inbar
authors.initials: I
authors.lastname: Plaschkes
authors.forename: Igor
authors.initials: I
authors.lastname: Perevozkin
authors.forename: Michael
authors.initials: M
authors.lastname: Gurevich
authors.forename: Riki
authors.initials: R
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002678:Chimera; D016568:Drugs, Generic / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D016568:Drugs, Generic; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate