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MyoScreen, a High-Throughput Phenotypic Screening Platform Enabling Muscle Drug Discovery

Authors :
Young, Joanne
Margaron, Yoran
Fernandes, Mathieu
Duchemin-Pelletier, Eve
Michaud, Joris
Flaender, Mélanie
Lorintiu, Oana
Degot, Sébastien
Poydenot, Pauline
Source :
Journal of Biomolecular Screening; September 2018, Vol. 23 Issue: 8 p790-806, 17p
Publication Year :
2018

Abstract

Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays. MyoScreen myotubes form aligned, striated myofibers, and they show nerve-independent accumulation of acetylcholine receptors (AChRs), excitation–contraction coupling (ECC) properties characteristic of adult skeletal muscle and contraction in response to chemical stimulation. Reproducibility and sensitivity of the fully automated MyoScreen platform are highlighted in assays that quantitatively measure myogenesis, hypertrophy and atrophy, AChR clusterization, and intracellular calcium release dynamics, as well as integrating contractility data. A primary screen of 2560 compounds to identify stimulators of myofiber regeneration and repair, followed by further biological characterization of two hits, validates MyoScreen for the discovery and testing of novel therapeutics. MyoScreen is an improvement of current in vitro muscle models, enabling a more predictive screening strategy for preclinical selection of the most efficacious new chemical entities earlier in the discovery pipeline process.

Details

Language :
English
ISSN :
10870571 and 1552454X
Volume :
23
Issue :
8
Database :
Supplemental Index
Journal :
Journal of Biomolecular Screening
Publication Type :
Periodical
Accession number :
ejs46323703
Full Text :
https://doi.org/10.1177/2472555218761102