title: In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5.
abstract: 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 defined as distinct based solely on amino acid sequence comparison, with a similarity cut-off of 2.5% difference. Ten subtypes have been identified for BoNT/A, which is the serotype associated with the most severe human botulism and also the most commonly used serotype for clinical purposes. Analyses of several of these subtypes have revealed distinct characteristics, ranging from differences in cell entry and enzyme kinetics to differences in potency in mice and cell-model specific potency. A long-term activity study in cultured primary neurons has indicated that BoNT/A1, 2, 4, and 5 have a similar duration of action, whereas BoNT/A3 has a significantly shorter duration of action. This report describes an in vivo mouse study, showing that after local injection BoNT/A2 resulted in faster onset of local paralysis than BoNT/A1, 3, 4, and 5, whereas BoNT/A3 resulted in significantly faster recovery of motor-neuron deficiency.
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA. Electronic address: sabine.pellett@wisc.edu.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pellett
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Tepp
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Regina C M
authors.initials: RC
authors.lastname: Whitemarsh
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Marite
authors.initials: M
authors.lastname: Bradshaw
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000145:classification / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009046:Motor Neurons / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: D019274:Botulinum Toxins, Type A
keywords: BoNT/A; Botulinum neurotoxin; Duration of action; Rotarod; Subtypes