In vitro models of neuromuscular junctions and their potential for novel drug discovery and development

• Published in: Expert opinion on drug discovery Vol. 15; no. 3; p. 307
• Main Authors: Vila, Olaia F, Qu, Yihuai, Vunjak-Novakovic, Gordana
• Format: Journal Article
• Language: English
• Published: England 03.03.2020
• Subjects: Animals; Drug Development - methods; Drug Discovery - methods; High-Throughput Screening Assays; Humans; Models, Biological; Motor Neurons - metabolism; Muscle Fibers, Skeletal - metabolism; Neuromuscular Diseases - drug therapy; Neuromuscular Diseases - physiopathology; Neuromuscular Junction - metabolism; Stem Cells - cytology; human stem cells; drug testing; Neuromuscular junction; bioengineering
• ISSN: 1746-045X
• DOI: 10.1080/17460441.2020.1700225

: Neuromuscular Junctions (NMJs) are the synapses between motor neurons and skeletal muscle fibers, and they are responsible for voluntary motor function. NMJs are affected at early stages of numerous neurodegenerative and neuroimmunological diseases. Due to the difficulty of systematically studying and manipulating NMJs in live subjects, systems with human tissue models would provide a powerful complement to simple cell cultures and animal models for mechanistic and drug development studies. : The authors review the latest advances in models of NMJs, from traditional cell co-culture systems to novel tissue culture approaches, with focus on disease modeling and drug testing. : In recent years, more sophisticated models of human NMJs have been established. The combination of human stem cell technology with advanced tissue culture systems has resulted in systems that better recapitulate the human NMJ structure and function, and thereby allow for high-throughput quantitative functional measurements under both healthy and diseased conditions. Although they still have limitations, these advanced systems are increasingly demonstrating their utility for evaluating new therapies for motoneuron and autoimmune neuromuscular diseases, and we expect them to become an integral part of the drug discovery process in the near future.