The Evolution of Stem Cells, Disease Modeling, and Drug Discovery for Neurological Disorders

Abstract

Human neurological disorders are amongst the most challenging areas of translational research. The difficulty of acquiring human neural samples or specific, representative animal models has necessitated a multifaceted approach to understanding disease pathology and drug discovery. The de-differentiation of somatic cells to human induced pluripotent stem cells (hiPSCs) for the generation of neural derivatives has broadened the capability of biomedical research to study human cell types in neurological disorders. The initial zeal for the potential of hiPSCs for immediate biomedical breakthroughs has evolved to more reasonable expectations. Over the past decade, hiPSC technology has demonstrated the capacity to successfully establish “disease in a dish” models of complex neurological disorders and to identify possible novel therapeutics. However, as hiPSCs are employed more broadly, an increased understanding of the limitations of hiPSC studies are becoming more evident. Here we review the challenges of studying neurological disorders, the current limitations of stem cell based disease modeling, and the degrees to which hiPSC studies to date have demonstrated the capacity to fill essential gaps in neurological research.