Botulinum Toxin: History, Mechanism of Action, Therapeutic Applications

Abstract

Botulinum toxin (BoNT) is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. The clinical syndrome of botulism can occur following ingestion of contaminated food, from colonization of the infant gastrointestinal tract, or from a wound infection. BoNT is broken into 7 neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. The German physician and poet Justinus Kerner first developed the idea of a possible therapeutic use of botulinum toxin, which he called "sausage poison". In 1973, Dr. Alan B. Scott used BoNT-A in monkey experiments; in 1980, he used BoNT-A for the first time in humans to treat strabismus. Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and the postganglionic sympathetic cholinergic nerves in the sweat glands and decreasing the release of acetylcholine. This mechanism laid the foundation for the development of the toxin as a therapeutic tool. (Archives of Neuropsychiatry 2010; 47 Supplement: 1-5)