DNA methylation changes in PBMCs of multiple sclerosis patients on glatiramer acetate therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE310754 | GEO | 2026/06/03
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:In order to investigate the effects of Glatiramer acetate (GA) in treatment-naïve RR-MS female patients’ B cells we performed Affymetrix Gene-Chip Human Genome HG-U133A_2 hybridization experiments Transcriptome analysis before and after acute (six hours in vitro) and chronic (six months in vivo) treatment with GA. We compared the transcriptional profiles of B cells, from the above-mentioned patients, treated or not with GA for 6 hours in vitro, and before and after six months of GA treatment in vivo.
2018-11-30 | GSE110023 | GEO
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: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
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.
2014-10-01 | GSE61901 | GEO
Project description:Long-term Glatiramer Acetate Treatment Induces Subtle Changes in Microglial Transcriptome
| PRJNA715728 | ENA
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. Glatiramoid samples for SPL cell activation were grouped into four categories: 1) Verified GA, which included GA-RS (22 samples) and GA drug product (GA-DP, 34 samples from 30 batches) manufactured by Teva; 2) Deliberately Modified GA (DM-GA; 9 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 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-NM-bM-^@M-^] 11 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 .
2013-08-01 | E-GEOD-40566 | biostudies-arrayexpress