Botulinum Neurotoxins

Botulinum Neurotoxins (BoNT's) are a family of thick-walled, heat-stable, highly potent toxins produced by the bacterium Clostridium botulinum and the related species C. butyricum and C. baratii. BoNT's are composed of a neurotoxic component (sometimes referred to as the 150 kD toxin) and one or more non-toxic components known as hemagglutinins or non-toxic proteins; both components are proteins. BoNT's block the release of acetylcholine at the neuromuscular junction, leading to a flaccid paralysis that affects muscles innervated by the affected neuron. The neurotoxic component of BoNT's is further divided into seven distinct serotypes (a, b, c (also known as d), e, f, g, h). Each serotype is antigenically distinct and has unique biological properties. BoNT's are potent inhibitors of acetylcholine release; they act by sequestering the vesicular form of the neurotransmitter in synaptic vesicles and preventing its release into the synapse upon binding to the medium-chain zinc-binding proteins known as synaptobrevin-2 and synaptotagmin. In this manner, BoNT's inhibit acetylcholine release between presynaptic and postsynaptic neurons. Inhibiting acetylcholine release from presynaptic axon terminals with BoNT's results in decreased muscle activity in the affected muscle, resulting in the flaccid paralysis that is observed. The duration of this paralysis is related to several factors, including the amount and type of BoNT injected, the dosage of BoNT, the muscle group affected, and the presence of physiologic conditions that may affect toxin uptake or action. BoNT's are highly selective toxins that, when used in clinical settings, performed at very low doses, can produce localized paralysis in a specified muscle or group of muscles with minimal systemic toxicity. BoNT's are most commonly used in the treatment of movement disorders, such as dystonia and spasticity, as well as cosmetic treatments such as treating wrinkles. They have also been found to be useful in the treatment of a number of conditions, such as migraine headaches, incontinence, excessive sweating, and jaw-clenching.