Abstract
Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.
Highlights
We describe their suitability for high-throughput studies including drug screenings aimed at identifying and evaluating novel Botulinum neurotoxins (BoNTs)-based therapeutics
All corresponds to a chimeric toxin, with its light chain (LC) similar to the LC of BoNT/F and its heavy chain (HC) sim serotypes differ in their toxicity, molecular site of action, efficiency in terms of muscle to the another new BoNT
To study BoNTs, preferential models have been developed over the years: in vivo, BoNT-induced muscle relaxation is assessed in mice and rats (MBA); BoNT potency was evaluated ex vivo on mice hemidiaphragms, measuring muscle contractility; and BoNT
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Botulism results in progressive flaccid paralysis of motor and autonomic nerves It was first described in the 1820s by Kerner, who presented a study on several patients suffering from fatal poisoning after ingestion of contaminated sausages. Human pluripotent stem cells (hPSCs) are characterized by two main cardinal properties: a capacity to give rise to all the cell type forming an organism, and the capacity to self-renew almost without any limitation When combined together, both properties of hPSCs offer, in theory, unlimited access to highly relevant cell source for a range of applications in drug discovery. Under many conditions, provide an alternative to the animal models generally used in the field [19]
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