NGP 555, a γ-Secretase Modulator, Lowers the Amyloid Biomarker, Aβ 42, in Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in Rodents.

Autor: Kounnas MZ; NeuroGenetic Pharmaceuticals, Inc., Del Mar, CA 92014., Lane-Donovan C; Department of Molecular Genetics, Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390., Nowakowski DW; N Molecular Systems, Inc., Palo Alto, CA 94303., Herz J; Department of Molecular Genetics, Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390., Comer WT; NeuroGenetic Pharmaceuticals, Inc., Del Mar, CA 92014.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (New York, N. Y.) [Alzheimers Dement (N Y)] 2017 Jan; Vol. 3 (1), pp. 65-73.
DOI: 10.1016/j.trci.2016.09.003
Abstrakt: Introduction: 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.
Methods: 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.
Results: 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.
Discussion: Abundant data support Aβ 42 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.
Competing Interests: Conflict of Interest: Drs. Comer and Kounnas are employees and shareholders of NeuroGenetic Pharmaceuticals, Inc.
Databáze: MEDLINE
Externí odkaz: