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MyoScreen, a High-Throughput Phenotypic Screening Platform Enabling Muscle Drug Discovery.
- Source :
-
SLAS discovery : advancing life sciences R & D [SLAS Discov] 2018 Sep; Vol. 23 (8), pp. 790-806. Date of Electronic Publication: 2018 Mar 02. - 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.
- Subjects :
- Biomarkers
Cell Culture Techniques
Cell Differentiation drug effects
Cell Line
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical methods
Excitation Contraction Coupling drug effects
Humans
Muscle Fibers, Skeletal cytology
Muscle Fibers, Skeletal drug effects
Muscle Fibers, Skeletal metabolism
Muscular Diseases drug therapy
Muscular Diseases etiology
Muscular Diseases metabolism
Regeneration drug effects
Biological Assay methods
Drug Discovery methods
High-Throughput Screening Assays
Muscle, Skeletal drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2472-5560
- Volume :
- 23
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- SLAS discovery : advancing life sciences R & D
- Publication Type :
- Academic Journal
- Accession number :
- 29498891
- Full Text :
- https://doi.org/10.1177/2472555218761102