Theoretical Analyses of the Functional Regions of the Heavy Chain of Botulinum Neurotoxin
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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The peptide neurotoxin from Clostridium botulinum botulinum neurotoxin type A BTX-A is perhaps the most lethal substance known. On the other hand, its extraordinary selectivity has been exploited in its use as a pharmacological research tool and as an exquisitely potent drug in the treatment of a variety of dystonias and other neurological disorders. A number of clinical reports of BTX-A administration have emphasized that BTX-A is safe and efficacious in the treatment of some of these conditions, while there is an occasional appearance of relatively benign toxin-induced symptoms. Several studies, however, have noted a low incidence of more serious complications e.g. , mild choking on fluids, distal muscle weakness and some patients may need to be considered at risk if subjected to this therapy. The occurrence of these symptoms in some patients suggests that the toxin is already internalized within the peripheral cholinergic nerve endings and is no longer susceptible to nonpenetrating neutralizing antibodies. This situation will become more complex if serotypes other than the now commonly used BTX-A enter the clinical arena.