Limitation of animal models in drug discovery and development Candice Tahimic, Ph.D. Hence, there is a need to use human cells to test the efficacy of candidate drugs.  Animal cells may not always simulate complex biochemical mechanisms of human disease  Is the observed disease phenotype in the animal equivalent to that of the human counterpart?

Midbrain dopaminergic neurons in the substantia nigra are selectively lost in Parkinson’s disease Human ES or iPS cells can be converted into dopaminergic neurons for use as cell models of Parkinson’s disease Certain psychiatric disorders and certain addictions (nicotine and cocaine dependence) are thought to be mediated by the dopaminergic system Candice Tahimic, Ph.D.

Human cell models for disease: the promise of hES/iPS cells F Test compound Reporter levels A B C D E “On-dish” assay for efficacy Chemical library screening Dirrected differentiation Candice Tahimic, Ph.D. Human ES cell Neurons The iPS or hESC -derived neurons are treated with a number of candidate drugs for a particular disease. The neurons are then observed for reversal of the disease phenotype. Promising test compounds are further validated.