(1041-B) Engineered human neuromuscular junction- on-a-chip platform as a drug development tool supporting development of therapies
Monday, February 5, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Currently available in-vitro models fail to reproduce the pathological complexities of most neuromuscular diseases, including Myasthenia gravis (MG), a rare autoimmune disease driven by autoantibodies targeting components of the neuromuscular junction (NMJ). For the successful development of new therapies, robust alternative approaches methods (NAMs) that specifically mimic the human NMJ function are required to elucidate the toxicity mechanism of autoantibodies in MG. In this study, the Ananda Devices microfluidic platform NeuroMuscle™ was used to create an in vitro 3D co-culture of motor neurospheres derived from human induced pluripotent cells and primary human skeletal muscle fibers that reproduces a functional NMJ. The NeuroMuscle™ platform is scalable, compatible with standard laboratory equipment and uses human derived reagents and cells. The platform was validated for robust detection of muscle contraction after stimulation with acetylcholine; reproducible detection of NMJ function by quantifying muscle contraction after neuronal stimulation with glutamate and rapid detection of NMJ function inhibition by alpha-bungarotoxin and D-tubocurarine. The impact of the platform was showcases as NeuroMuscle™ accelerated the discovery and approval of treatment of MG patients. The NMJ cultures in the NeuroMuscle™ platform were incubated with sera from healthy and MG patients which induced complement activation and impaired neurotransmission. The data highlight how Ananda Devices’ human based, in vitro, NeuroMuscle™ platform supports drug discovery in NMJ-related diseases and could be used to test compounds to understand efficacy and mechanistic rationale.