4.7 Article

Glatiramer acetate treatment effects on gene expression in monocytes of multiple sclerosis patients

Journal

JOURNAL OF NEUROINFLAMMATION
Volume 10, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/1742-2094-10-126

Keywords

Glatiramer acetate; Relapsing-remitting multiple sclerosis; Monocytes; Gene expression profiling; Microarray analysis

Funding

  1. Teva Pharmaceutical Industries Ltd.
  2. United Europeans for the development of PHArmacogenomics in Multiple Sclerosis (UEPHA*MS) consortium, Marie Curie Initial Training Network

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Background: Glatiramer 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. Methods: Monocytes 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. Results: More 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. Conclusions: Overall, 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.

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