Tugnoli_1997_Expert.Opin.Investig.Drugs_6_1383

Since Alan Scott's research, botulinum toxin (BoNT) has been used in several diseases or conditions characterised by muscular overactivity. BoNT acts on either neuromuscular or autonomic cholinergic junctions. Seven different serotypes are known, with antigenic specificity and different therapeutic profiles. BoNT is made up of a heavy chain, involved in binding and membrane translocation, and a light chain, involved in blocking neuroexcytosis. Each serotype shares a specific acceptor on the presynaptic membrane of a cholinergic junction. The available BoNT preparations differ in toxicity, purity and stability. Injection of the neurotoxin produces several modifications at a neuromuscular junction. Axonal sprouting, muscular fibre atrophy, and new end-plates are the most evident histological events after BoNT treatment. They appear to be reversible in untreated muscles. Diffusion can occur at first by haematogeneous or local BoNT spread. Several factors, such as dose, volume, site of injection, muscle size, and muscular fascia, can influence the amount of diffusion and possible side-effects. After prolonged BoNT treatment patients can become unresponsive. Antibodies directed against BoNT have been observed with ELISA or mouse bioassay. Different serotypes have been used to treat non-responder patients. Novel toxins with lower immunogenicity and prolonged clinical efficacy are required for more effective treatment.