Scientific Background

Clostridium botulinum (Fig. 5.1) produces eight serologically distinct botulinum toxins designated A, B, Cα, Cβ, D, E, F, G. Of the eight serotypes, A is the most potent, although serotypes B and F are almost as strong.These proteins are activated by complexing with hemagglutinin and the nontoxic molecule. A dimer forms, and activity is caused by the resulting inhibition of acetylcholine release from presynaptic neurons at the neuromuscular junction (NMJ). The inhibition takes place as the neurotoxin cleaves SNAP-25 proteins and ultimately leads to the chemical denervation at the motor end plate. Symptoms are characterized by striated muscle relaxation that usually begins 2–3 days after local injection. Relaxation is correlated with the amount of natural purified protein delivered. With exposure to increasing amounts, the relaxation may ultimately progress to total relaxation by 8–10 days postinjection. Although this process of chemical denervation is complete in all exposed NMJs, neurogenesis leads to recovery of the muscle in almost every situation. Denervation effects are generally inactivated in 3–6 months [1].

Fig. 5.1. Chemical structure of botulinum toxin A

Botulinum toxin is an immunogenic protein and is capable of producing neutralizing and nonneutralizing antibodies. Treatment failure and eventual attenuation of the therapeutic effects may be traced to this immunogenic response. Fortunately, antibodies to one serotype of the botulinum protein do not cross-neutralize another, so an option for continuing therapy may be to change to another serological type [1]. For individuals treated for cosmesis or hyperhidrosis, the development of resistance has not been a problem.However,neutralizing antibodies have been reported in 3–5% of patients treated for dystonia [2, 3, 4].