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- W2029895715 abstract "Botulinum neurotoxicity is characterized by peripheral neuromuscular blockade/flaccid paralysis that can lead to respiratory failure and ultimately death. Current therapeutic options provide relief in a pre-exposure scenario, but there are no clinically approved postexposure medical countermeasures. Here, we introduce a platform that utilizes a combination of a toxin sequestering agent and a pharmacological antagonist to ablate botulinum neurotoxicity in a well-defined mouse lethality assay. The platform was constructed to allow for ready exchange of sequestering agent and/or pharmacological antagonist for therapeutic optimization. As such, we attempted to improve upon the pharmacological antagonist, a potassium channel blocker, 3,4-diaminopyridine, through a prodrug approach; thus, a complete kinetic decomposition pathway is described. These experiments provide the first proof-of-principle that a synergistic combination strategy can be used to reduce toxin burden in the peripheral using a sequestering antibody, while restoring muscle action via a pharmacological small molecule antagonist." @default.
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- W2029895715 date "2014-07-11" @default.
- W2029895715 modified "2023-09-29" @default.
- W2029895715 title "A Platform Stratifying a Sequestering Agent and a Pharmacological Antagonist as a Means to Negate Botulinum Neurotoxicity" @default.
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- W2029895715 doi "https://doi.org/10.1021/cn500135h" @default.
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