Traditional drug discovery often begins with simple biochemical and transformed cellular models, advances to more complex animal models in late discovery phases, and often does not ‘see’ appropriate human biology until clinical trials. While widely deployed, this process can result in initial hits that do not translate to the clinic and ultimately lead to late-stage failures while running counter to the emerging standard in animal use of replace, reduce, and refine.

Advances in human induced pluripotent stem cells (iPSCs), three-dimensional (3D) culture technologies, combined with advanced analytical methods offer solutions for these shortcomings. Initiating the drug discovery process with disease-based human iPSC-derived 3D cultures and high-throughput assays for rapid compound screening and multi-parametric analysis of biological signals enables a faster and more accurate drug discovery pipeline with novel target identification, improved hit efficacy and safety, and ultimately increased clinical success all while reducing animal use.

This presentation will:

1) discuss how a human iPSC-derived 3D-neurospheroid in vitro screening platform can reduce, replace, and refine animal use in pre-clinical research

2) utilize a case study with Rett Syndrome iPSC-derived neurospheroids to demonstrate rapid target and hit identification/validation

3) provide an example of clinical translation for the neurospheroid platform

Learning Objectives:

1. Deploying advanced human culture systems in phenotypic screening

2. Key elements for a successful phenotypic screen using human iPSC-derived neurospheroids