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Nervous System Diseases

Endocrinology and Metabolic Disease

Single-chain FV antibody fragment

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Endocrinology and Metabolic Disease	1
Nervous System Diseases	1

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Single-chain FV antibody fragment	1

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α-synuclein(Synuclein alpha)	1

Triggering receptor expressed on myeloid cells 2 (TREM2) is type I transmembrane protein receptor found in osteoclasts, dendritic cells, macrophages, and microglia.In the central nervous system, TREM2 expressionis confined exclusively to microglia. TREM2 comprises an extracellular V-type Ig (Ig) ectodomain, a connecting stalk followed by a transmembrane region and a short C-terminal tail.TREM2 signaling involves its association with the adaptor proteins DAP10 and DAP12 with the recruitment of PI3K and SYK, resp. that drive multiple downstream events resulting in Ca²⁺ mobilization and activation of mitogen-activated protein kinase-mediated cascades as well as other pathways.The downstream signals result in the modulation of key functional properties of the macrophage/microglia including proliferation, phagocytosis, survival, actin cytoskeleton remodeling, and cell metabolism

05 Jun 2023·Cells

TREM2 Agonism with a Monoclonal Antibody Attenuates Tau Pathology and Neurodegeneration.

Article

Author: Benaim, Clara ; George, Jacob ; Fassler, Michael

TREM2 is a membrane receptor expressed on microglia that plays a pivotal role in the organization and function of these innate immune cell components within the neurodegenerated brain. Whereas TREM2 deletion has been studied extensively in experimental beta-amyloid and Tau-based models of Alzheimer's disease, its engagement, and subsequent agonism have not been tested in the context of Tau pathology. Herein, we explored the effects of Ab-T1, an agonistic TREM2 monoclonal antibody on Tau uptake, phosphorylation, seeding, and spreading as well as its therapeutic efficacy in a Tauopathy model. Ab-T1 enhanced the uptake of misfolded Tau to microglia and induced a non-cell autonomous attenuation of spontaneous Tau seeding and phosphorylation in primary neurons from human Tau transgenic mice. Ex vivo, incubation with Ab-T1 led to a significant reduction in the seeding of Tau pathology in the hTau murine organoid brain system. Systemic administration of Ab-T1 resulted in reduced Tau pathology and propagation when hTau was stereotactically injected into the hemispheres of hTau mice. Intraperitoneal treatment with Ab-T1 lead to attenuation of cognitive decline in the hTau mice that was associated with reduced neurodegeneration and synaptic preservation with amelioration of the global neuroinflammatory program. Collectively, these observations show that TREM2 engagement with an agonistic antibody result in reduced Tau burden concomitant with attenuated neurodegeneration ascribed to the education of resident microglia. These results may suggest that despite the opposing results with regard to the effect of TREM2 knockout in experimental Tau-based model systems, receptor engagement and activation by Ab-T1 appears to possess beneficial effects with respect to the various mechanisms mediating Tau-driven neurodegeneration.

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100 Translational Medicine associated with Cognyxx Pharmaceuticals, Inc

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Pipeline

Pipeline Snapshot as of 21 Dec 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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