PT  - JOURNAL ARTICLE
AU  - Bruno Boivin
AU  - Kasper C.D. Roet
AU  - Xuan Huang
AU  - Kyle W. Karhohs
AU  - Mohammad H. Rohban
AU  - Jack Sandoe
AU  - Ole Wiskow
AU  - Rie Maeda
AU  - Alyssa Grantham
AU  - Mary K. Dornon
AU  - Jenny Shao
AU  - Devlin Frost
AU  - Dylan Baker
AU  - Kevin Eggan
AU  - Anne E. Carpenter
AU  - Clifford J. Woolf
TI  - A Multiparametric Activity Profiling Platform for Neuron Disease Phenotyping and Drug Screening
AID  - 10.1101/2021.06.22.449195
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.22.449195
4099  - http://biorxiv.org/content/early/2021/06/23/2021.06.22.449195.short
4100  - http://biorxiv.org/content/early/2021/06/23/2021.06.22.449195.full
AB  - Patient stem cell-derived models enable imaging of complex disease phenotypes and the development of scalable drug discovery platforms. Current preclinical methods for assessing cellular activity do not, however, capture the full intricacies of disease-induced disturbances, and instead typically focus on a single parameter, which impairs both the understanding of disease and the discovery of effective therapeutics. Here, we describe a cloud-based image processing and analysis platform that captures the intricate activity profile revealed by GCaMP fluorescent recordings of intracellular calcium changes and enables discovery of molecules that correct 153 parameters that define the amyotrophic lateral sclerosis motor neuron disease phenotype. In a high-throughput screen we identified compounds that revert the multiparametric disease profile to that found in healthy cells, a novel and robust measure of therapeutic potential quite distinct from unidimensional screening. This platform can guide the development of therapeutics that counteract the multifaceted pathological features of diseased cellular activity.Competing Interest StatementThe authors declare the following competing financial interests: Kasper C.D. Roet, Kevin Eggan, and Clifford J. Woolf are founders of QurAlis Corporation.