Glatiramer Acetate modulates ion channel expression and calcium homeostasis in B-cell of patients with relapsing-remitting multiple sclerosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110023 | GEO | 2018/11/30
REPOSITORIES: GEO
Similar Datasets
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: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: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:In this study, we investigated the therapeutic potential of a well-tolerated immunomodulatory relapsing-remitting multiple sclerosis drug, glatiramer acetate (GA), on the 3xTg mouse model of Alzheimer's Disease. Briefly, we treated aged female 3xTg mice (>15 mo) weekly with 0.1 mg of GA for 8 weeks. We were able to observe an improvement in cognition and amelioration of amyloid pathology, which we attempted to correlate with changes in microglial transcriptome. To this end, we sorted microglia (CD45int CD11b+) from the hippocampi of GA or PBS-treated 3xTg mice for bulk RNA-seq.
2021-08-27 | GSE169216 | GEO
Project description:For decades, policies regarding generic medicines have sought to provide patients with economical access to safe and effective drugs, while encouraging the development of new therapies. This balance is becoming more challenging for physicians and regulators as biologics and non-biological complex drugs (NBCDs) such as glatiramer acetate demonstrate remarkable efficacy, because generics for these medicines are more difficult to assess. We sought to develop computational methods that use transcriptional profiles to compare branded medicines to generics, robustly characterizing differences in biological impact. We combined multiple computational methods to determine whether differentially expressed genes result from random variation, or point to consistent differences in biological impact of the generic compared to the branded medicine. We applied these methods to analyze gene expression data from mouse splenocytes exposed to either branded glatiramer acetate or a generic. The computational methods identified extensive evidence that branded glatiramer acetate has a more consistent biological impact across batches than the generic, and has a distinct impact on regulatory T cells and myeloid lineage cells. In summary, we developed a computational pipeline that integrates multiple methods to compare two medicines in an innovative way. This pipeline, and the specific findings distinguishing branded glatiramer acetate from a generic, can help physicians and regulators take appropriate steps to ensure safety and efficacy. Glatiramoid samples for SPL cell activation were grouped into four categories: 1) Verified GA, which included GA-RS (22 biological samples) and GA drug product (GA-DP, 34 biological samples from 30 batches) manufactured by Teva; 2) Deliberately Modified GA (DM-GA; 9 biological samples), which included glatiramoids made by Teva that were similar to GA but modified in a variety of ways: prepared with different ingredients (e.g., missing a constituent amino acid); prepared with the same amino acids in the same molar ratio as GA, but with defined amino acid sequences and different molecular weights (referred to as peptide markers TV-35 and TV-66); synthesized by a different process (e.g., changing acetolytic cleavage conditions, alternating polymerization initiator); exposed to destabilizing conditions (e.g., degradation by acid, base, and heat); 3) Unverified Glatiramoids, which included 4 biological samples, TV-5010 and 3 glatiramoids synthesized to be similar to GA but not manufactured using the Teva-patented manufacturing process; and 4) Unverified Generic GA, which included samples from 2 glatiramoids (M-bM-^@M-^\GA-QM-bM-^@M-^] 11 biological samples from 5 different batches, and 2 M-bM-^@M-^\GA-CM-bM-^@M-^] samples from a single batch) marketed as generic GA manufactured by companies other than Teva.
2014-10-01 | E-GEOD-61901 | 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.
2009-08-01 | GSE16214 | GEO
Project description: Not available
| S-EPMC6464642 | biostudies-literature
Project description:DNA methylation is a universal epigenetic mechanism involved in the regulation of gene expression in both normal physiological conditions and various pathologies. It has been demonstrated that the development of multiple sclerosis (MS) is accompanied by significant alterations in DNA methylation profiles in the blood immune cells of patients. Studies investigating genome-wide DNA methylation changes during therapy for MS patients using immunomodulatory drugs are limited, and for glatiramer acetate (GA), such investigations have not been conducted at all.
2026-06-03 | GSE310754 | GEO
Project description: Not available
| S-EPMC3174971 | biostudies-literature