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

Introduction: 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, in vitro systems with human tissue models would provide a powerful complement to simple cell cultures and animal models for mechanistic and drug development studies.Areas covered: The authors review the latest advances in in vitro models of NMJs, from traditional cell co-culture systems to novel tissue culture approaches, with focus on disease modeling and drug testing.Expert opinion: In recent years, more sophisticated in vitro 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.