Myriad Uses of Botulinum Toxin

Botulinum toxin (BTX) is an endotoxin produced by Clostridium botulinum, a gram-positive anaerobic bacterium1. Seven serotypes of botulinum toxin (BonT) are known and these are labeled as types A, B, C (Cl, C2, D, E, F, and G. These are structurally similar. BonT molecule is synthesized as a single chain (150 Kd) and then cleaved to form the dichain molecule with a disulfide bridge. The light chain (~50 Kd -with amino acids 1-448) acts as a zinc (Zn ++) endopeptidase similar to tetanus toxin with proteolytic activity located at the N-terminal end. The heavy chain (~100 Kd-amino acids 449-1280) provides cholinergic specificity and binding of the toxin to presynaptic receptors, and promotes light chain translocation across the endosomal membrane. The discovery by Burgen et al, in 19492 that botulinum toxin blocks neuromuscular transmission provided theoretical foundation for the development of the toxin as a therapeutic tool. The clinical use of purified botulinum toxin (BonT) represents one of the most dramatic role reversals in modern medicine: a potential evil transformed into a health benefit and now used widely as a therapeutic agent in an expanding scope of human conditions. The discussion will focus on the myriad uses of BonT type A, the serotype commercially available for clinical use. Clinical experience is emerging also with BTX types B 3 and F4.