Glatiramer Acetate modulates ion channel expression and calcium homeostasis in B-cell of patients with relapsing-remitting multiple sclerosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110023 | GEO | 2018/11/30
REPOSITORIES: GEO
Similar Datasets
Project description:One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-β), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms. We used microarrays to capture gene expression profile of untreated subjects and of subjects under disease modyfing treatment (Interferon Beta and Glatiramer Acetate), in order to correlate gene expression and genotype data and in order to identify sets of genes specifically regulated in the different treatment categories.
2009-08-01 | GSE16214 | GEO
Project description:The purpose of this study was to analyze the transcriptional effects induced by glatiramer acetate treatment (GA; Copaxone, 20 mg injected subcutaneously once daily) in blood monocytes of patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of monocytes from 8 MS patients within the first two months of GA administration.
2012-12-07 | GSE42763 | GEO
Project description:The purpose of this study was to analyze the transcriptional effects induced by glatiramer acetate treatment (GA; Copaxone, 20 mg injected subcutaneously once daily) in blood monocytes of patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of monocytes from 8 MS patients within the first two months of GA administration. EDTA blood samples were taken from all patients immediately before first and second GA injection as well as after 1 week, 1 month and 2 months. Total RNA of CD14+ monocytes isolated by magnetic-activated cell sorting (MACS) from each sample was extracted, labeled and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays to quantify the mRNA levels. This GEO entry provides the U133 Plus 2.0 microarray data.
2012-12-07 | E-GEOD-42763 | biostudies-arrayexpress
Project description:One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-β), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms. We used microarrays to capture gene expression profile of untreated subjects and of subjects under disease modyfing treatment (Interferon Beta and Glatiramer Acetate), in order to correlate gene expression and genotype data and in order to identify sets of genes specifically regulated in the different treatment categories. Experiment Overall Design: Between July 2002 and October 2007, PBMC samples were collected from relapsing-remitting MS subjects and CIS subjects as part of the Comprehensive Longitudinal Investigation of MS at the Brigham & Womenâs Hospital (CLIMB study). We then selected the first time point for each subject with multiple measurements based on an at least three months of treatment criteria. We thereafter analyzed the data for each treament category.
2009-08-09 | E-GEOD-16214 | biostudies-arrayexpress
Project description:Multiple sclerosis (MS) is a chronic and progressive neurological disease. MS is characterized by early-stage neuroinflammation, neurodegeneration, and demyelination, with a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. The currently unsatisfied availability of diagnostic and prognostic biomarkers concerning disease progression and treatment response represents an important requirement for therapy individualization and drug efficacy. Specific Disease Therapies (DMTs) are available to prevent MS-related brain damage; however, the specific drug choice is still under debate and needs further characterization. Since differentially expressed miRNAs have been proposed as diagnostic tools in neurodegenerative/neuro-inflammatory diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, we characterized the miRNA expression profiling in peripheral blood mononuclear cells (PBMC) of subjects with relapsing-remitting MS treated with high efficacy DMTs: Cladribine (CLA, n=11 patients) or Ocrelizumab (OCRE, n=14 patients). The treated patients were compared to control (CTR) untreated subjects (n=15). Blood samples were collected from patients before treatment (time t0) and 6 months post-treatment (time t1), but just once from control subjects. CLA drug tablets were administered to the selected relapsing-remitting MS patients with a dosage of 1.75 mg/kg given for 5 days. OCRE drug was administered to the other relapsing-remitting MS patients by infusion with a dosage of 300 mg, twice in two weeks.
2024-01-03 | GSE230064 | GEO
Project description: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 antiinflammatory 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. Cells from a human monocyte cell line (THP-1) were stimulated with either branded GA, purported generics from several manufacturers including Probioglat by ProbioMed, or vehicle control (mannitol) for 6, 12, or 24h. RNA was extracted and expression profiled genome-wide using the Affymetrix U133 Plus 2.0 chip. Four batches of GA and one batch of Probioglat were comparatively tested in six biological replicates each.
2015-05-22 | E-GEOD-68527 | biostudies-arrayexpress
Project description:Glatiramer Acetate modulates ion channel expression and calcium homeostasis in B-cell of patients with relapsing-remitting multiple sclerosis
| PRJNA432575 | ENA
Project description: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 antiinflammatory 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.
2015-05-22 | GSE68527 | GEO
Project description:Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer-acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases.
2024-07-09 | PXD053395 | Pride
Project description:Glatiramer acetate (GA; Copaxone), is a complex mixture of synthetic polypeptides approved for treatment of multiple sclerosis (MS). GA is an altered peptide ligand (APL) of myelin basic protein (MBP), an encephalitic autoantigen implicated in MS. GA induces GA-reactive T cells, which upregulate expression of anti-inflammatory and neurotrophic substances in the CNS. The antigenic sequences in glatiramoids cannot be completely characterized; nevertheless, differences among them can cause toxicity. We conducted microarray analyses to determine whether gene expression by GA-reactive lymphocytes from mouse spleens could differentiate GA from other glatiramoids. Expression of 135 genes was unique to cells reactivated by GA vs by intentionally altered GA and other glatiramoids. Significantly (p<0.01) altered expression of 207 genes was observed by cells reactivated by GA vs purported generic GA. Some APLs of MBP have caused serious adverse effects in MS patients. The influence of altered gene expression on glatiramoid safety warrants further investigation.
2013-08-01 | GSE40566 | GEO