RRPV BoNT-NMJ

Botulinum neurotoxins (BoNT/A’G) inhibit acetylcholine release at the neuromuscular junction through cleavage of SNARE proteins (e.g., SNAP-25, VAMP, syntaxin). Currently, BoNT characterization, including toxin potency and neutralization by medical countermeasures, is measured using mouse-based bioassays, primarily the Mouse Potency Assay (MPA) and Mouse Neutralization Assay (MNA), respectively. There is increasing scientific, ethical, and regulatory interest in transitioning to human-relevant in vitro systems that can provide mechanistic insight while reducing reliance on animal testing. NMJ micro-physiological systems may provide a biologically relevant platform capable of measuring BoNT potency and evaluating countermeasure efficacy. BARDA is interested in understanding whether NMJ-based in vitro platforms could support future development of validated assays capable of reducing and potentially replacing reliance on mouse bioassays for BoNT potency and neutralization measurements, with specific interest in systems that can show recovery of neuronal signaling and thereby be appropriate for medical countermeasures evaluation.