Progressive multiple sclerosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA966951 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification of early neurodegenerative pathways in progressive multiple sclerosis
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Project description:Novel Biomarkers and Interferon Signature in Secondary Progressive Multiple Sclerosis
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Project description:Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.
2015-10-06 | GSE73608 | GEO
Project description:Siponimod selectively enriched regulatory T and B lymphocytes in active secondary progressive multiple sclerosis patients: 20 SPMS baseline including 3 repeats, 19 treated with 5 placebo and 14 siponimod treated.
2020-04-07 | GSE141381 | GEO
Project description:Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand–receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.
2022-06-05 | PXD026529 | Pride
Project description:Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand–receptor interactions in local microenvironments we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and CNS disease models, supporting their causal role and value as potential therapeutic targets for progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue, that facilitate this debilitating disease.
2022-05-12 | GSE174647 | GEO
Project description:Transcriptome analysis of RNA samples from human PBMCs of IFN-beta-1a (Rebif) therapy in secondary progressive multiple sclerosis (SPMS) patients. Objective: Untreated multiple sclerosis is inflammatory, with decreased immune control and subnormal type I interferon (IFN) signaling. IFN-ß therapy corrects abnormal IFN-ß signaling, reduces inflammation on MRI, exacerbations, and disease worsening in relapsing-remitting MS (RRMS). For unclear reasons, secondary progressive MS (SPMS) exhibits waning attacks, relentless neurodegeneration, and diminished benefits of therapy. Methods: Peripheral blood mononuclear cells and serum were from 10 healthy controls (HC), 9 therapy-naive RRMS, 20 therapy-naïve SPMS, and 10 IFN-ß-treated SPMS patients after therapy washout and four hours after IFN-ß-1a injection. Global gene expression was assayed with sensitive RNA microarrays and multiplexed serum immune and neuroprotective protein assays. Results: Therapy-naive RRMS cells displayed 8,723 differentially expressed genes (DEG), compared to HC, vs. d only 3,936 DEG in therapy-naive SPMS. In SPMS, gene expression was subnormal in the WNT/ß-catenin pathway that suppresses inflammation and enhances blood-brain barrier integrity. Olfactory receptor (OR) genes, linked to lymphocyte migration, were overexpressed in RRMS (111 DEG), intermediate in SPMS (34 DEG) vs. HC, differentiating RRMS from SPMS (p < 0.007). IFN-ß injections in SPMS decreased expression of pro-inflammatory genes and increased anti-inflammatory, anti-oxidant metallothionein genes. Pro-inflammatory and anti-inflammatory protein levels were balanced in HC, disrupted in RRMS, and intermediate in SPMS. Interpretation: Aberrant gene expression seen in RRMS wanes in SPMS, paralleling fewer clinical exacerbations and diminished therapeutic responses. Novel biomarkers for SPMS suggest new targets to correct subnormal immune regulation and brain repair in this neurodegenerative disease.
2024-03-07 | GSE247181 | GEO
Project description:One of the most challenging aspects in multiple sclerosis (MS) research is to understand the mechanisms leading to neurodegeneration and subsequent tissue repair. Here, we aimed to identify biomarkers associated with the progressive phases of the disease that may have neuroprotective potential. To achieve this, we performed a bioinformatic approach integrating transcriptional and proteomic profiles obtained during the course of experimental autoimmune encephalomyelitis (EAE) combined with gene expression microarray data from neuronal differentiation. Integrative analysis of omics data identified two molecules, serine (or cysteine) peptidase inhibitor, clade A, member 3N (Serpina3n) and S100 calcium binding protein A4 (S100A4), as biomarkers up-regulated in chronic progressive EAE whose expression was also induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of Serpina3n and S100A4 during EAE as reflected by their co-localization with β-III-Tubulin in neurons from cerebellum, hippocampus and spinal cord tissues during EAE. Finally, levels of SERPINA3, the human ortholog of murine Serpina3n also known as α1-antichymotrypsin, and S100A4 were increased in cerebrospinal fluid of MS patients compared with non-inflammatory neurological controls. However, only SERPINA3 showed differences across MS clinical forms and levels were significantly elevated in patients with progressive forms of the disease, particularly in patients with primary progressive MS, compared with relapsing-remitting MS and neurological controls. Altogether, these results point to a role of SERPINA3 as biomarker associated with the progressive forms of MS that may also have neuroregenerative potential
2021-02-01 | PXD018173 | Pride
Project description:Transcriptional abnormalities in iPSC-derived oligodendrocytes of individuals with primary progressive multiple sclerosis
| PRJNA871916 | ENA