Effect of Potent γ-Secretase Modulator in Human Neurons Derived From Multiple Presenilin 1–Induced Pluripotent Stem Cell Mutant Carriers

摘要

ImportanceAlthough considerable effort has been expended developing drug candidates for Alzheimer disease, none have yet succeeded owing to the lack of efficacy or to safety concerns. One potential shortcoming of current approaches to Alzheimer disease drug discovery and development is that they rely primarily on transformed cell lines and animal models that substantially overexpress wild-type or mutant proteins. It is possible that drug development failures thus far are caused in part by the limits of these approaches, which do not accurately reveal how drug candidates will behave in naive human neuronal cells.