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

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

Author information

1
Teva Pharmaceutical Industries, Petach Tikva, Israel.
2
Immuneering Corporation, Cambridge, MA, USA. Electronic address: skolitz@immuneering.com.
3
Immuneering Corporation, Cambridge, MA, USA.
4
Teva Pharmaceutical Works Ltd., Hungary.
5
Teva Pharmaceutical Industries, Petach Tikva, Israel. Electronic address: Iris.Grossman@teva.co.il.

Abstract

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

PMID:
26711576
DOI:
10.1016/j.jneuroim.2015.11.020
[Indexed for MEDLINE]
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