Identification of antibody repertoires in atracurium hypersensitivity for novel diagnostics and therapies – CURAREP2

NeuroMuscular Blocking Agents (NMBA; curares) relax skeletal muscles to facilitate surgeries and permit intubation, but lead to adverse reactions: (a) severe hypersensitivity reactions (anaphylaxis) thought to rely on pre-existing anti-NMBA antibodies; (b) complications due to postoperative residual curarization. Identification of patients at risk remains suboptimal due to the lack of adequate tools to detect anti-NMBA antibodies. Rocuronium, an aminosteroid, and atracurium, a benzylisoquinoline, are the most prevalent NMBAs worldwide. A capturing agent – sugammadex – exists for two NMBAs, rocuronium and its derivative vecuronium, allowing reversal of profound curarization. However, no capture reagent exists for atracurium. Based on strong preliminary results, our project proposes to characterize anti-atracurium antibody repertoires in patients with atracurium-anaphylaxis, describe activation pathways leading to anaphylaxis, develop and validate diagnostic and therapeutic molecules to ameliorate patient screening and reverse profound neuromuscular block.