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
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
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
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
All Roads Lead to TREM2: Gearing Up to Target This Receptor Since the discovery of rare, yet potent risk variants in the TREM2 gene 11 years ago, the microglial receptor has emerged as a pivot point in the pathogenesis of Alzheimer’s disease Findings presented at the International Conference on Alzheimer’s and Parkinson’s Diseases, held March 28 to
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
A tetravalent TREM2 agonistic antibody reduced amyloid . . . - ALZFORUM Zhao P, Xu Y, Jiang L, Fan X, Li L, Li X, Arase H, Zhao Y, Cao W, Zheng H, Xu H, Tong Q, Zhang N, An Z A tetravalent TREM2 agonistic antibody reduced amyloid pathology in a mouse model of Alzheimer's disease Sci Transl Med 2022 Sep 7;14 (661):eabq0095 PubMed
TREM2, humanized (R47H) X 5XFAD - ALZFORUM Summary The R47H variant of TREM2 has been found to confer an approximately threefold greater risk for Alzheimer’s disease in humans heterozygous for this allele To study the effects of the R47H variant in the context of amyloidosis, mice carrying a human TREM2 gene were crossed with 5XFAD mice Compared with mice expressing the common variant of human TREM2, mice expressing the R47H