Botulinum Neurotoxins

Abstract

Eight antigenically distinguishable botulinum neurotoxin serotypes, BoNT/A-H, have been identified. In 2013, a new serotype, type H, was identified. All serotypes exert their neurotoxic effect by blocking motor neuron release of acetylcholine via BoNT light chain cleavage of the SNARE complex required for synaptic vesicle fusion. There are three main products containing BoNT/A under various trade names on the market: Botox^®/Vistabel^®, Dysport^®/Azzalure^®, and Xeomin^®/Bocouture^®. Botox^® is a 900 kDa complex with one molecule of BoNT/A; Xeomin^® contains only pure BoNT/A. Recognizing the differences between botulinum toxin products on the market, and in an attempt to reduce the potential for errors, the FDA in 2009 issued name changes by adding the prefixes, ona-, abo-, inco-, and rima-, to each of the former botulinum toxin names. For example, botulinum toxin type A became onabotulinumtoxinA. Approved indications for botulinum toxin preparations include urinary incontinence, upper limb spasticity, cervical dystonia, headaches in migraine patients, hyperhidrosis, blepharospasm associated with dystonia, strabismus, hemifacial spasm, and glabellar and lateral canthal lines. A boxed warning draws attention to the spread of toxin from the injection site, including swallowing and breathing difficulties, leading to death. Adverse toxin effects include urinary retention, dysphagia, respiratory tract infection, flu syndrome, neck and musculoskeletal pain, headache, dysphonia, injection site discomfort, and eyelid ptosis. An antibody response to the toxin may occur. Such antibodies may, or may not, affect the biological activity. Employment of purified toxin may potentially reduce the rate of secondary treatment failure.