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The clinical effects of botulinum toxin have been recognised since the end of the 19th century. It is the most potent neurotoxin known and it is produced by the gram negative anaerobic bacteriumClostridium botulinum. The paralytic effect of the toxin is due to blockade of neuromuscular transmission.1 Injection into a muscle causes chemodenervation and local paralysis and this effect has led to the development of the toxin as a therapeutic tool. It is now used clinically for a wide range of conditions,2particularly focal dystonias, and increasingly for spasticity. This paper reviews the mode of action of botulinum and focuses on its use in the management of spasticity.
There are seven immunologically distinct serotypes of botulinum toxin (labelled A-G). This review concentrates on the only type in routine clinical use—type A (BTX-A). Currently, type B,3 4type C,5 and type F6-8are being investigated for clinical use and type B may be available in the near future.
Botulinum toxin acts at the neuromuscular junction by inhibiting the release of acetylcholine. It acts selectively on peripheral cholinergic nerve endings causing chemical denervation after the binding, internalisation, and activation of the toxin at the neuromuscular junction. The toxin is synthesised as a relatively inactive single polypeptide chain.
Selective high affinity binding of BTX-A occurs at the neuromuscular junction. After internalisation, it is activated when its structure is modified by cleavage of the disulfide bond linking the light and heavy chain. The N terminal of the heavy chain then promotes penetration and translocation of the light chain across the endosomal membrane into the cytosol. This then interacts with, and cleaves the fusion protein SNAP 25 (synaptosomal associated protein) inhibiting the calcium mediated release of acetylcholine from the presynaptic nerve terminal.9 10 Nerve sprouting and muscle re-innervation …
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