Human in vitro disease models to aid pathway and target discovery for neurological disorders

Abstract

Abstract Mouse model systems of human neurological disorders though useful are not always accurate because mouse and human brains have considerable differences in development, genetics, and physiology. They vary considerably in their embryonic brain development and organogenesis. At the genome level, there are substantial differences, particularly in the regulatory regions. Lastly, the two organisms differ in their organ functions. Thus many drugs, which are successfully validated in animal models, do not translate well to humans. So the need for in vitro human disease model systems is surmounting to recapitulate cellular and molecular features of human disorders adequately and to devise therapeutic strategies for treating them. The advent of iPSC technology has revolutionized the way we study monogenic, polygenic, and complex genetic disorders, including both neurodevelopmental and neurodegenerative diseases. Their abilities to self-renew, differentiate into any cell type in the body, and generate in large numbers make them very suitable for studying cellular and molecular aspects of diseases and for drug screening and cell therapies. In this chapter, I delineate how iPSCs are being used for disease modeling to identify pathways and targets for drug development.