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Trialists Grapple with How to Outsmart TREM2 | ALZFORUM Series - AD PD™ 2025: Advances in Science Therapy: Part 1 of 15: Finally, PET Tracers For α-Synuclein Yield Signal in Idiopathic Parkinson’s Part 2 of 15: New Partnership Forms to Harness AI for Alzheimer’s Research Part 3 of 15: Moving Target: New Biology Casts TREM2 as a Shifty Mark Part 4 of 15: TREM2: A Chill Pill for Neurons? Part 5 of 15: Trialists Grapple with How to Outsmart
VG-3927 | ALZFORUM In September 2023, VG-3927 became the first small-molecule TREM-2 agonist cleared to enter the clinic In October 2023, the first volunteer was treated in a Phase 1, placebo-controlled, single- and multiple-ascending-dose safety study being conducted in Miami
Moving Target: New Biology Casts TREM2 as a Shifty Mark Series - AD PD™ 2025: Advances in Science Therapy: Part 1 of 15: Finally, PET Tracers For α-Synuclein Yield Signal in Idiopathic Parkinson’s Part 2 of 15: New Partnership Forms to Harness AI for Alzheimer’s Research Part 3 of 15: Moving Target: New Biology Casts TREM2 as a Shifty Mark Part 4 of 15: TREM2: A Chill Pill for Neurons? Part 5 of 15: Trialists Grapple with How to Outsmart
TREM2: A Chill Pill for Neurons? | ALZFORUM TREM2 created quite the buzz at this year’s AD PD meeting, held April 1-5 in Vienna In the wake of a TREM2 agonist’s demise, scientists presented optimistic findings from early phase trials of a fresh batch of agonists Juxtaposing this were presentations that unveiled a new modus operandi for
TREM2 R47H - ALZFORUM Ghani M, Sato C, Kakhki EG, Gibbs JR, Traynor B, St George-Hyslop P, Rogaeva E Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set
TREM2 | ALZFORUM Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor of the innate immune system expressed on microglia, macrophages, dendritic cells, and osteoclasts TREM2 is a member of the immunoglobulin superfamily Endogenous ligands of this receptor are unknown but when triggered, it signals through the transmembrane adapter protein TYROBP DAP12 to activate phagocytosis of pathogens
TREM2 - ALZFORUM TREM2 encodes Triggering Receptor Expressed on Myeloid Cells 2, a transmembrane receptor that modulates microglial activity and survival TREM2 variants cause Nasu-Hakola disease (NHD), a rare autosomal recessive early-onset dementia, and may modify the risk of developing Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis
DNL919 - ALZFORUM Background This TREM2 agonist antibody activates microglia to phagocytose amyloid DNL919 contains a transferrin-receptor binding sequence engineered into its Fc domain Thus, the antibody binds to the abundant transferrin receptors on endothelial cells of the blood-brain barrier, which facilitate its active transport into the brain
Ferried Into Brain, TREM2 Antibody Stirs Microglia | ALZFORUM TREM2 antibody sports transferrin receptor binding domain to ease entry into brain It activated microglia and boosted brain glucose metabolism The antibody is in a first Phase 1 trial
TREM2 Cleavage Site Pinpointed: A Gateway to New Therapies? TREM2 binds anionic lipids released during neuronal and glial damage It supports microglial metabolism and it promotes the migration, cytokine release, phagocytosis, proliferation, and survival of the cells (Aug 2017 news; Feb 2015 news) Evidence suggests that TREM2 spurs microglia to form a neuroprotective barrier around amyloid plaques and to clear Aβ (May 2016 news; Jul 2016 news