Abstract

iPSC-Based Physiologically Relevant Disease Modeling for CNS Drug Discovery and Neurotoxicity Screening

Jason Lo, Account Manager (EU + UK), Applied StemCell, Inc.

An iPSC-based approach to modeling human diseases provides an unlimited source of physiologically relevant in vitro tools for basic and applied research, with potential applications in personalized regenerative medicine. Unlike primary cells, iPSCs are amenable to CRISPR/Cas9 genome editing, thereby enabling the generation of numerous cell line models for hard-to-source and hard-to-model diseases, especially neurological disorders.  Further differentiation of these genome edited iPSCs and their isogenic matched controls (parental line) into somatic lineages provides a controlled in vitro platform to investigate disease phenotypes, and for drug discovery and screening. This talk elaborates on the workflow involved in generating biorelevant iPSC models of neurological disorders such as Parkinson’s Disease, its differentiation into neural lineages, and suitability as a preclinical platform for screening potential drug candidates for efficacy and neurotoxicity, including assays to determine the specificity of different neural cell types for a small range of chemicals and drugs from the Tox21 library, as well as for neuroprotective assays with dopaminergic neurons.