Botulinum toxin, also called “miracle poison,” is one of the most poisonous biological substances known.[1] It is a neurotoxin produced by the bacterium Clostridium botulinum, an anaerobic, gram-positive, spore-forming rod commonly found on plants, in soil, water and the intestinal tracts of animals.

Uses

Scott[2] first demonstrated the effectiveness of botulinum toxin type A for the management of strabismus in humans. Subsequently, botulinum toxin was approved for the treatment of numerous disorders of spasticiy[1] and a host of other conditions. Currently it is used in almost every sub-specialty of medicine. In 2002, the FDA approved the use of Botox? (Botulinum toxin-A) for the cosmetic purpose of temporarily reducing glabeller forehead frown lines.

Mechanism of action

All the serotypes interfere with neural transmission by blocking the release of acetylcholine, which is the principal neurotransmitter at the neuromuscular junction. Intramuscular administration of botulinum toxin acts at the neuromuscular junction to cause muscle paralysis by inhibiting the release of acetylcholine from presynaptic motor neurons. Botulinum toxins act at four different sites in the body: The neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings that release acetylcholine.[2]

Production

Botulinum toxin is produced under anaerobic conditions by Clostridium botulinum. There are seven types of toxin (A–G), each coded for by a phage (Ecklund, Poysky and Reed, 1972). The early designation of a C2 subtype of toxin has been abandoned with the recognition that this toxin, now called the binary toxin, is not a cause of botulinum-type neuromuscular dysfunction. All types of botulinum toxin have a molecular weight of 150000 kilodaltons; each is synthesized as a single polypeptide that subsequently undergoes‘nicking’ by endogenous or exogenous proteases to form two chains connected by a disulphide bridge. The toxin appears to bind to specific arrangements of sialic acid residues. For example, certain gangliosides, notably GT1b and GD1b, greatly decrease neurotoxicity in vivo following preincubation (Simpson and Rapport, 1971; Kitamura, Iwamori and Nagai, 1980). It is likely that the botulinum receptor is either a neuronal membrane ganglioside, or a glycoprotein that shares a similar carbohydrate moiety.

References

[1].Münchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ. 2000;320:161–5. doi: 10.1136/bmj.320.7228.161.

[2] P K Nigam,  Anjana Nigam. “Botulinum toxin.” Indian Journal of Dermatology 55 1 (2010): 8–14.