Development of Treatments for Intoxication by Botulinum Neurotoxin

摘要

The botulinum neurotoxins (BoNTs) consist of seven immunologically distinct protein toxins secreted by the anaerobic bacteria Clostridium botulinum, Clostridium baratti and Clostridium butyricum (Simpson, 1981; 1989; Sellin, 1981). The median human lethal dose has been estimated to be 1 ng/kg, making BoNT the most lethal substance known to mankind (Schantz and Sugiyama, 1974; Franz, 1997). Intoxication by BoNT leads to flaccid paralysis that is bilateral and descending, involving primarily skeletal muscle but also structures innervated by autonomic fibers (Habermann and Dreyer, 1986; Simpson, 1989; Shapiro et al., 1998). Botulism becomes fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Franz et al., 1993), or when patients succumb to secondary infections following long periods of intensive care (Hatheway et al., 1984; Shapiro et al., 1998). Human intoxication is generally caused by exposure to serotypes A, B, E and to a much lesser extent to serotype F, and is manifested as foodborne, wound or infant botulism (Habermann and Dreyer, 1986; Simpson, 1981; 1989).