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Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE241217 | GEO | 2024/12/05

REPOSITORIES: GEO

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Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain - Study 2

Project description:Monkeys were treated with a single i.v 200 mg/kg dose of hPara.09 or Anti-gD (Isotype control). Brain was harvested on days 4 and 28, and RNA was extracted from the cerebral cortex. The following groups are included: Group 1: Day 4 gD 200mg/kg n=6; Group 2: Day 4 hPara.09 200 mg/kg n=6; Group 3: Day 28 gD 200mg/kg n= 6; Group 4: Day 28 hPara.09 200 mg/kg n=6 (24 animals total). To assess expression heterogeneity between brain samples, 2 different frontal cortex punches were taken from each monkey, resulting in 48 total samples.

2024-12-05 | GSE246092 | GEO

Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [bulk RNA-seq]

Project description:In order to search for pharmacodynamic biomarkers of a TREM2 agonist antibody (Para09) in primates we performed bulk RNA-Seq on cortical tissue from cynomolgus monkeys after single IV injected doses. Changes in proliferation genes such as MKI67 were observed, as well as genes associated with glial activation, such as CHI3L1. This experiment demonstrates that our antibody induces transcriptional changes in the brain after peripheral administration.

2024-12-05 | GSE236453 | GEO

Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [single nuclei RNA sequencing]

Project description:In order to search for pharmacodynamic biomarkers of a TREM2 agonist antibody (Para09) in primates we performed single nuclei RNA-Seq on cortical tissue from cynomolgus monkeys after single IV injected doses. Changes in proliferation genes such as MKI67 were observed, as well as genes associated with glial activation, such as CHI3L1. This experiment demonstrates that our antibody induces transcriptional changes in the brain after peripheral administration.

2024-12-05 | GSE241190 | GEO

Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain

Project description:Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain

| PRJNA1006736 | ENA

Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain - Study 2

Project description:Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain - Study 2

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Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [bulk RNA-seq]

Project description:Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [bulk RNA-seq]

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Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [single nuclei RNA sequencing]

Project description:Transcriptional Responses to TREM2 Agonist Antibody Treatment in Cynomologus Monkey Brain [single nuclei RNA sequencing]

| PRJNA1006707 | ENA

SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-24 | GSE236928 | GEO

A blood-brain barrier transport vehicle improves brain biodistribution of a TREM2 antibody and enhances microglial metabolism via receptor clustering

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-11-23 | GSE200276 | GEO

Expression data of iPS microglia treated with TREM2 agonist antibody

Project description:Loss-of-function variants of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of developing Alzheimer's disease (AD). The mechanism through which TREM2 contributes to the disease (TREM2 activation vs inactivation) is largely unknown. Here, we analyzed changes in a gene set downstream of TREM2 to determine whether TREM2 signaling is modified by AD progression. We generated an anti-human TREM2 agonistic antibody and defined TREM2 activation in terms of the downstream expression changes induced by this antibody in microglia developed from human induced pluripotent stem cells (iPSC). Differentially expressed genes (DEGs) following TREM2 activation were compared with the gene set extracted from microglial single nuclear RNA sequencing data of patients with AD, using gene set enrichment analysis. We isolated an anti-TREM2-specific agonistic antibody, Hyb87, from anti-human TREM2 antibodies generated using binding and agonism assays, which helped us identify 300 upregulated and 251 downregulated DEGs. Pathway enrichment analysis suggested that TREM2 activation may be associated with Th2-related pathways. TREM2 activation was lower in AD microglia than in microglia from healthy subjects or patients with mild cognitive impairment. TREM2 activation also showed a significant negative correlation with disease progression. Pathway enrichment analysis of DEGs controlled by TREM2 activity indicated that TREM2 activation in AD may lead to anti-apoptotic signaling, immune response, and cytoskeletal changes in the microglia. We showed that TREM2 activation decreases with AD progression, in support of a protective role of TREM2 activation in AD. In addition, the agonistic anti-TREM2 antibody can be used to identify TREM2 activation state in AD microglia.

2021-09-15 | GSE159333 | GEO

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