A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

著者: Kelsie M. LaBarbera, Yvette I. Sheline, Nicholas J. Izzo, Carla M. Yuede, Lora Waybright, Raymond Yurko, Hannah M. Edwards, Woodrow D. Gardiner, Kaj Blennow, Henrik Zetterberg, Anne Börjesson‐Hanson, Roger Morgan, Charles S. Davis, Robert Guttendorf, Lon S. Schneider, Steven T. DeKosky, Harry LeVine, Michael Grundman, Anthony O. Caggiano, John R. Cirrito, Susan M. Catalano, Mary E. Hamby - Translational Neurodegeneration 2023 被引用: 28

NCT03522129 https:// clini caltr ials.gov/ ct2/ show/ NCT03 522129.Investigational therapies for Alzheimer's disease (AD) target a wide range of mechanisms, yet promising disease-modifying therapies remain a huge unmet need.Much evidence indicates that the oligomeric form of amyloid-beta (Aβ) is a toxic species contributing to AD through synaptic damage and neuronal toxicity [1].In support of this, Aβ oligomer reduction in an AD mouse model leads to memory preservation [2, 3], and clinical benefit was observed in trials of lecanemab, which targets Aβ oligomers and protofibrils [4], in AD patients, encouraging the continued development of Aβ oligomertargeting therapies.CT1812 is a novel, small-molecule, brain-penetrant sigma-2 receptor (S2R) modulator that selectively prevents and displaces Aβ oligomers from binding to neuronal synapses, thereby mitigating downstream toxicity.This is thought to occur through allosteric modulation