Industrial Production and Therapeutic Application of Botulinum Neurotoxin: The Role of C. botulinum Type A

Abstract: Botulinum neurotoxin has remarkably transitioned from a food safety hazard and biological warfare to an effective therapeutic drug. Currently, botulinum neurotoxins have seven serotypes (BoNT/A-G) in the form of protein complexes produced by Clostridium, a gram-positive and sporeforming bacteria. The conversion of toxins into useful drug substances of choice using the biotechnological process is tremendously increasing. Recent studies have shown that Botulinum neurotoxin-A (BoNT/A) has different biological activities and potencies in experimental and clinical conditions. They also indicate that the manufacturing process influences the potency and efficacy of BoNT/A drugs. Thus, this review focuses on the following criteria: detailed Fed-batch operation that includes the upstream and downstream processing of BoNT/A, the underlying mechanism behind the neurotoxic effect, and commercially available FDA-approved BoNT/A products and their therapeutic uses. Still, some research gaps exist in the mechanism for the treatment of psychiatric disorders.