Clinical use of botulinum neurotoxins.

Abstract

Botulinum neurotoxin (BoNT) is the most potent biologic toxin known to a man (Gill 1982). Its clinical effects have been recognized since the end of the nineteenth century, when van Ermengem (1897) related botulism to a toxin produced by Clostridium botulinum, an anaerobic bacterium. The analysis of botulism outbreaks has led to the recognition that human intoxication may be caused by BoNT types A, B, E, and F (Green et al. 1983; Sakaguchi 1983). There are three other antigenically distinct toxins (C, D, and G) (Simpson 1981). These serotypes are produced by distinct strains of C. botulinum (Schantz and Johnson 1992). Although outbreaks of botulism have been identified as recently as in 1989 (Critchley et al. 1989), in the past two decades medical interest in BoNT has been fueled by the demonstration of its therapeutic usefulness. In 1973 Scott used BoNT type A for treatment of strabismus in nonhuman primates, and 8 years later he reported the results of his initial experience with this toxin to correct strabismus in humans (Scott 1981). Since then BoNT injections have been demonstrated to be a safe and efficient therapy for a large number of neurologic and nonneurologic diseases (Jankovic and Brin 1991). In December 1989 the United States Food and Drug Administration approved BoNT type A for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients 12 years of age and older.