Abstract

Evaluation of Dug Efficacy using Human Neuronal Cells Derived from Patient Induced Pluripotent Stem Cells

Wei Zheng, Group Leader, National Institute of Health

Although animal disease models are extensively used for the evaluation of drug efficacy in the drug discovery process, many human diseases are not recapitulated well by animal models. The species difference between human and animals often causes different disease phenotypes between these two groups. It is estimated that more than half of the failure of experimental drugs is due to lack of clinical efficacy in humans, regardless of their activities observed in animal models. Recent advances in induced pluripotent stem (iPS) cell technology enable the generation of patient iPS cells and mature human cells such as neuronal cells, cardiomyocytes, and hepatocytes. These pathological and disease-phenotype related cell types derived from patient iPS cells should be better model systems for evaluation of drug efficacies and prediction of clinical outcomes. We have generated a number of iPS cell lines from patient primary cells and evaluated drug efficacies using the patient-iPS cell differentiated neuronal cells for several diseases. We found that the patient iPS cell-derived neuronal cells more accurately predicted drug efficacy and potency compared to primary patient fibroblasts. Additional results and experience will be discussed and shared in this presentation.