Screening of candidate analgesics using a patient-derived human iPSC model of nociception identifies putative compounds for therapeutic treatment
Summary
Utilisation of human iPSCs for efficient differentiation into sensory neuron-like cells offers a novel strategy for studying pain mechanisms. IEM sensory neuron-like cells exhibit key biomarkers and generate action potentials in response to noxious stimulation. IEM sensory neuron-like cells display spontaneous electrical activity, providing a relevant nociceptive model. Screening of 281 compounds identified four candidates that significantly reduced spontaneous firing with low cytotoxicity. Electrophysiological profiling of selected compounds revealed promising insights into their mechanisms of action, specifically modulating the NaV 1.7 channel for targeted analgesia. © 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
| Authors | Thornton JR, Capurro A, Harwood S, Henderson TC, Unsworth A, Görtler F, Nagaraja-Grellscheid S, Telezhkin V, Lako M, Sernagor E, Armstrong L |
|---|---|
| Journal | Clinical and translational medicine |
| Publication Date | 2025 May;15(5):e70339 |
| PubMed | 40415465 |
| PubMed Central | PMC12104564 |
| DOI | 10.1002/ctm2.70339 |