Abstract

Phenotypic Screening with iPSC-Sensory Neuron Excitability Assays

Darren Cawkill, Associate Director, Pfizer

For Pain research, use of phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing key functional endpoint measurements that have a direct link with disease. However, recent work at Pfizer’s UK-based Neusentis research site has resulted in the successful generation of hiPSC-derived sensory neurons at a robust production scale; a process that has been used to supply neurons for assay development from both normal donors and pain (Erythromelalgia) patients. This presentation will provide an overview of how these cell types have been used for phenotypic assay development and validation together with a summary of ongoing screening initiatives. Progress towards the main goal of identifying new targets/pathways/MOA for modulating neuronal excitability will be outlined alongside data to show that patient-derived hiPSC-neurons demonstrate a spontaneous excitable phenotype that can be used for disease-relevant screening without the need for any exogenous stimulus.