Abstract

BackgroundGlatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to investigate the effects of GA therapy on the gene expression of monocytes.MethodsMonocytes were isolated from the peripheral blood of eight RRMS patients. The blood was obtained longitudinally before the start of GA therapy as well as after one day, one week, one month and two months. Gene expression was measured at the mRNA level by microarrays.ResultsMore than 400 genes were identified as up-regulated or down-regulated in the course of therapy, and we analyzed their biological functions and regulatory interactions. Many of those genes are known to regulate lymphocyte activation and proliferation, but only a subset of genes was repeatedly differentially expressed at different time points during treatment.ConclusionsOverall, the observed gene regulatory effects of GA on monocytes were modest and not stable over time. However, our study revealed several genes that are worthy of investigation in future studies on the molecular mechanisms of GA therapy.

Highlights

  • Glatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS)

  • This study focused on the in vivo effects of GA therapy on the gene expression of monocytes, which are the precursors of macrophages and dendritic cells

  • There is a lack of transcriptome studies on the effects of GA in Multiple sclerosis (MS) patients

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Summary

Introduction

Glatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). GA is not a defined chemical substance, but a standardized mixture of synthetic peptides These peptides are made up of four different amino acids, glutamic acid, lysine, alanine and tyrosine (G-L-A-T), in a molar ratio of 1.5:3.6:4.6:1.0, assembled in a random order into polypeptide chains with a length of 40 to 100 residues [7]. This mixture of peptides was initially intended to mimic myelin basic protein (MBP) and to induce experimental autoimmune encephalomyelitis (EAE), the animal model of MS [8]. GA has been wellestablished for MS therapy for more than a decade due to its beneficial clinical effects and its favorable safety profile

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