Elizabeth D. Buttermore

Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research Elizabeth D. Buttermore

Drug discovery in the neurosciences has struggled in recent years to lead to identification of novel therapeutics for patients with varying indications, including epilepsy, chronic pain, and psychosis. Current treatment options for such patients are decades old and offer little relief with many side-effects. One explanation for this lull in novel therapeutics is a lack of novel target identification for neurological disorders and target identification requires exemplar preclinical data. To improve on the preclinical work that often relies on rodent modelling, the field has begun utilizing patient-derived induced pluripotent stem cells (iPSCs) to differentiate neurons in vitro for preclinical characterization of neurological disease and target identification. Due to the perceived promise of this technology, there has been a recent boom in the number of researchers working with induced pluripotent stem cells (iPSCs) to model neurological disorders. This boom has led to the development of state-of-the-art techniques for differentiating and phenotyping patient-derived neurons. However, there has yet to be standardization of methodology across institutions, leading to unreproducible data.

Phenotyping Human iPSC-derived Neurons: Patient-Driven Research examines the steps in a preclinical pipeline that utilizes iPSC-derived neuronal technology and what considerations and best practices should be implemented for success and reproducibility. By using example projects in ALS and epilepsy as a template, the text allows readers to understand what considerations are important to assess at the start of project design. It addresses the reproducibility issues at each stage of the pipeline and provides suggestions for improvement. From patient sample collection and proper controls, to neuronal differentiation, phenotyping, and screening, detailed descriptions of each stage of the pipeline will help everyone, regardless of which stage of the pipeline they are most experienced, better understand the requirements of the entire pipeline.