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. Conclusion: GA-induced functional pathways coincide with known mechanisms of GA activity in MS patients and further support the unique therapeutic effect of this drug.
Original language | English |
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Pages (from-to) | 351-362 |
Number of pages | 12 |
Journal | Expert Opinion on Therapeutic Targets |
Volume | 17 |
Issue number | 4 |
DOIs | |
State | Published - 1 Apr 2013 |
Keywords
- Functional pathways
- Gene expression
- Glatiramer acetate
- Glatiramoid
- Microarray
- T cells
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Clinical Biochemistry