Human models as new tools for drug development and precision medicine

Despite advances in drug discovery and development, treatments for neurological and mental health disorders still suffer from poor efficacy, high toxicity, and high attrition rates. This stems from intrinsic pitfalls of the current preclinical models used to test novel compounds. For example, animal models cannot replicate human genetics, the diversity of human brain cells, or certain aspects of human metabolism. The best models for drug development are those that can account for the effects that genetic and environmental diversity may have on basic tissue biology, at the same time being reproducible and accurately reflecting drug responses. Emerging technologies involving human pluripotent stem cells show great promise for developing such reliable, rapid, and cost-effective models to precisely reflect the diversity of human disease and responses to therapeutic agents that cannot be recapitulated in animals. Here we review some of these models and how they are starting to revolutionize the drug development pipeline.