title: Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids.
abstract: Glatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated, and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GA's biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated anti-inflammatory markers (e.g. IL10), and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA. Key results were verified using qRT-PCR. Genes (e.g. CCL5, adj. p < 4.1 × 10(-5)) critically involved in pro-inflammatory pathways (e.g. response to lipopolysaccharide, adj. p = 8.7 × 10(-4)) were significantly induced by Probioglat compared with branded GA. Key genes were also tested and confirmed at the protein level, and in primary human monocytes. These observations suggest differential biological impact by the two glatiramoids and warrant further investigation.
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kolitz
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Hasson
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Towfic
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Funt
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bakshi
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: Daphna
authors.initials: D
authors.lastname: Laifenfeld
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Augusto
authors.initials: A
authors.lastname: Grinspan
authors.affiliation: Immuneering Corporation, Cambridge, MA, USA.
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Birnberg
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Rivka
authors.initials: R
authors.lastname: Schwartz
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: Liat
authors.initials: L
authors.lastname: Hayardeny
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.
authors.forename: Iris
authors.initials: I
authors.lastname: Grossman
mesh_terms: D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D000068717:Glatiramer Acetate / Q000494:pharmacology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D000068717:Glatiramer Acetate; D020782:Matrix Metalloproteinases