title: Functional effects of the antigen glatiramer acetate are complex and tightly associated with its composition.
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.
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Hasson
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA. Electronic address: skolitz@immuneering.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kolitz
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Towfic
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Laifenfeld
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bakshi
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Beriozkin
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Shacham-Abramson
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Bracha
authors.initials: B
authors.lastname: Timan
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Fowler
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Birnberg
authors.affiliation: Teva Pharmaceutical Works Ltd., Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Konya
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Arthur
authors.initials: A
authors.lastname: Komlosh
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Ladkani
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Zeskind
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel. Electronic address: Iris.Grossman@teva.co.il.
authors.forename: Iris
authors.initials: I
authors.lastname: Grossman
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000068717:Glatiramer Acetate / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D013154:Spleen / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate
keywords: Gene expression; Glatiramer acetate; Microarray; Multiple sclerosis; Therapeutic equivalence