NGP 555, a γ-Secretase Modulator, Lowers the Amyloid Biomarker, Aβ42, in Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in Rodents

Alzheimer's & Dementia : Translational Research & Clinical Interventions
Maria Z KounnasWilliam T Comer

Abstract

Alzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years. Using amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques we investigate the properties of NGP 555, a clinical-stage γ-secretase modulator. NGP 555 shifts amyloid peptide production to the smaller, non-aggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies. Abundant data support Aβ42 as a target for prophylactic or early-stage intervention therapies in AD. The γ-secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety.

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Citations

Jul 17, 2019·ChemMedChem·Guilherme Martins SilvaCarlos Henrique Tomich de Paula da Silva
Jan 11, 2020·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Maria Z KounnasWilliam T Comer
Oct 9, 2019·Journal of Alzheimer's Disease : JAD·Ahmed Morsy, Paul C Trippier
Mar 22, 2019·Pharmaceuticals·Miguel A Maia, Emília Sousa
Sep 29, 2020·Frontiers in Aging Neuroscience·Christiana BjorkliIoanna Sandvig
May 16, 2020·Oxidative Medicine and Cellular Longevity·Md Sahab UddinMohamed M Abdel-Daim
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Jul 23, 2021·ACS Chemical Neuroscience·Ángel SantiagoLaura Dominguez
Aug 27, 2021·Journal of Drug Targeting·Yang XieLinhong Ning

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Methods Mentioned

BETA
ELISA
ELISAs
transgenic

Software Mentioned

Pro Plus
Pro
Image
AutoDock Vina
NDP
Graphpad

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