title: Persistence of botulinum neurotoxin a subtypes 1-5 in primary rat spinal cord cells.
abstract: Botulinum neurotoxins (BoNTs) are the most poisonous substances known and cause the severe disease botulism. BoNTs have also been remarkably effective as therapeutics in treating many neuronal and neuromuscular disorders. One of the hallmarks of BoNTs, particularly serotype A, is its long persistence of 2-6 months in patients at concentrations as low as fM or pM. The mechanisms for this persistence are currently unclear. In this study we determined the persistence of the BoNT/A subtypes 1 through 5 in primary rat spinal neurons. Remarkably, the duration of intracellular enzymatic activity of BoNT/A1, /A2, /A4 and /A5 was shown to be at least 10 months. Conversely, the effects of BoNT/A3 were observed for up to ∼5 months. An intermittent dosing with BoNT/E showed intracellular activity of the shorter acting BoNT/E for 2-3 weeks, followed by reoccurrence and persistence of BoNT/A-induced SNAP-25 cleavage products.
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
authors.forename: Regina Clare Meyer
authors.initials: RC
authors.lastname: Whitemarsh
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
authors.forename: William Howard
authors.initials: WH
authors.lastname: Tepp
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
authors.forename: Eric Arthur
authors.initials: EA
authors.lastname: Johnson
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pellett
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000145:classification / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D042541:Intracellular Space / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D013997:Time Factors
chemical_list: D050825:Synaptosomal-Associated Protein 25; D019274:Botulinum Toxins, Type A