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Botulinum neurotoxins (BoNTs) are the most toxic substances known to mankind and are the causative agents of the neuroparalytic disease botulism. Their ease of production and extreme toxicity have caused these neurotoxins to be classified as Tier 1 bioterrorist threat agents and have led to a sustained effort to develop countermeasures to treat intoxication in case of a bioterrorist attack. While...
To date, over 40 subtypes of botulinum neurotoxins (BoNTs) have been identified. BoNTs are classified into 7 serotypes distinguished primarily by their antigenic properties, but also characterized by their unique SNARE targets and cleavage sites, host specificity, and duration of action. Sequencing efforts in the last decade have identified several subtypes within the serotypes. Subtypes are currently...
Botulinum Neurotoxin type D (BoNT/D) causes periodic outbreaks of botulism in cattle and horses, but is rarely associated with human botulism. Previous studies have shown that humans responded poorly to peripheral injection of up to 10U of BoNT/D. Isolated human pyramidalis muscle preparations were resistant to BoNT/D, whereas isolated human intercostal muscle preparations responded to BoNT/D similarly...
We developed a recombinant mAb-based antitoxin to treat botulism resulting from any subtype of botulinum neurotoxins type A, B, or E. Peripheral blood lymphocytes from botulinum toxoid immunized humans were used to create single chain Fv (scFv) yeast displayed antibody libraries. BoNT/A, B, and E binding human scFv antibodies were generated by selecting the libraries on BoNTs by using flow cytometry...
Clostridium botulinum neurotoxins (BoNTs) A and B are widely used as pharmaceuticals to treat various neurologic disorders and in cosmetic applications. The mouse lethality method is widely accepted for assay of therapeutic preparations of BoNTs, but it has well-known drawbacks including wide variability, the need for a large number of animals, and 2–4 days time requirements. We present a primary...
Clostridium botulinum comprises a diverse assemblage of clostridia that have the common property of producing a distinctive protein neurotoxin (BoNT) of similar pharmacological activity and extraordinary potency. BoNTs are produced in culture as molecular complexes consisting of BoNT, hemagglutinin (HA) and associated subcomponent proteins, nontoxic nonhemagglutinin (NTNH), and RNA. The genes encoding...
Although the ld 50 has been used to quantify the biologically active toxin in clinical preparations of botulinum A toxin (Botox and Dysport ), a discrepancy exists between the botulinum A toxin for multiple clinical indications. Our laboratory previously reported that a regional chemodenervation assay in the mouse could be utilized to detect the difference in the potencies of the...
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