Botulinum Toxin: A Successful Therapeutic Protein

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Abstract
Botulinum toxin serotype A has proven to be a successful and valuable therapeutic protein when dosage, frequency of treatment and variety of treated clinical conditions are considered. This modern therapeutic protein was predicted by Justinus Kerner, a 19th century German physician, who provided the first detailed clinical description of botulism and its association with faulty sausage production [5-7]. Kerner was preceded by Paracelsus, who described the duality of a drug as “only the dose makes a remedy poisonous” [7]. This concept is well known to modern medicinal chemists, pharmacologists and clinicians worldwide. Because botulinum toxin is an enzyme and specifically delivered to its target cell / neuron, exceedingly small doses are needed to exert its pharmacological effect. Botulinum toxin therapy is successful because of the local administration of nanogram quantities of this highly selective and long-lasting (months) therapeutic effect, which leads to symptomatic relief of numerous disease conditions. These minute therapeutic doses are dramatically lower than the doses needed to cause systemic disease (e.g. botulism). This review will focus on the current understanding of the mechanism of action of botulinum neurotoxins and the pharmacology of the various approved-marketed products and the direction of future research.

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