Functional effects of the antigen glatiramer acetate are complex and tightly associated with its composition

J Neuroimmunol. 2016 Jan 15:290:84-95. doi: 10.1016/j.jneuroim.2015.11.020. Epub 2015 Nov 24.


Glatiramer acetate (Copaxone®; GA) is a non-biological complex drug for multiple sclerosis. GA modulated thousands of genes in genome-wide expression studies conducted in THP-1 cells and mouse splenocytes. Comparing GA with differently-manufactured glatiramoid Polimunol (Synthon) in mice yielded hundreds of differentially expressed probesets, including biologically-relevant genes (e.g. Il18, adj p<9e-6) and pathways. In human monocytes, 700+ probesets differed between Polimunol and GA, enriching for 130+ pathways including response to lipopolysaccharide (adj. p<0.006). Key differences were confirmed by qRT-PCR (splenocytes) or proteomics (THP-1). These studies demonstrate the complexity of GA's mechanisms of action, and may help inform therapeutic equivalence assessment.

Keywords: Gene expression; Glatiramer acetate; Microarray; Multiple sclerosis; Therapeutic equivalence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Cell Line
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glatiramer Acetate / chemistry*
  • Glatiramer Acetate / pharmacology*
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / drug effects
  • Monocytes / physiology
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Spleen / drug effects*
  • Spleen / physiology*


  • Adjuvants, Immunologic
  • Immunosuppressive Agents
  • Glatiramer Acetate