Drug discovery and development are among the most important translational science activities that contribute to treating and curing human diseases. However, the drug attrition rate is very high: it is estimated that only 1% of the initially tested compounds make it to the market. Main reasons are the lack of understanding of the pathological mechanisms and the scant predictability of the pre-clinical models used. There is a clear need for the use of more physiologically relevant disease models that recapitulate the profile of human diseases in vitro and bring higher predictability to the early phases of drug discovery.
Induced pluripotent stem cell (iPSC) technology is a powerful tool to bring the human biological context earlier into the drug discovery funnel and mitigate late-stage failures due to safety or efficacy concerns.
Human iPSC-derived disease models are of great advantage because they retain patient-specific genetic backgrounds and recapitulate many clinical features of human pathology. Nonetheless, significant expertise is required to overcome some technical and conceptual challenges for the widespread implementation of these models in the pharmaceutical industry.
Benefits and examples of successful disease models based on human iPSCs
The impact of human iPSC-derived disease models in drug discovery
Key considerations for the successful generation and application of iPSC-derived disease models in high-throughput phenotypic screening