1. Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients.
- Author
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Kutschenko A, Weisemann J, Kollewe K, Fiedler T, Alvermann S, Böselt S, Escher C, Garde N, Gingele S, Kaehler SB, Karatschai R, Krüger THC, Sikorra S, Tacik P, Wegner F, Wollmann J, Bigalke H, Wohlfarth K, and Rummel A
- Subjects
- Adult, Animals, Humans, Male, Mice, Muscle, Skeletal physiology, Treatment Outcome, Botulinum Toxins administration & dosage, Botulinum Toxins, Type A administration & dosage, Muscle, Skeletal drug effects, Neuromuscular Agents administration & dosage
- Abstract
Objectives: Botulinum neurotoxin serotypes A and B (BoNT/A & B) are highly effective medicines to treat hyperactive cholinergic neurons. Due to neutralizing antibody formation, some patients may become non-responders. In these cases, the serotypes BoNT/C-G might become treatment alternatives. BoNT/D is genetically least related to BoNT/A & B and thereby circumventing neutralisation in A/B non-responders. We produced BoNT/D and compared its pharmacology with BoNT/A ex vivo in mice tissue and in vivo in human volunteers., Methods: BoNT/D was expressed recombinantly in E. coli, isolated by chromatography and its ex vivo potency was determined at mouse phrenic nerve hemidiaphragm preparations. Different doses of BoNT/D or incobotulinumtoxinA were injected into the extensor digitorum brevis (EDB) muscles (n = 30) of human volunteers. Their compound muscle action potentials were measured 11 times by electroneurography within 220 days., Results: Despite a 3.7-fold lower ex vivo potency in mice, a 110-fold higher dosage of BoNT/D achieved the same clinical effect as incobotulinumtoxinA while showing a 50% shortened duration of action., Conclusions: BoNT/D blocks dose-dependently acetylcholine release in human motoneurons upon intramuscular administration, but its potency and duration of action is inferior to approved BoNT/A based drugs., Significance: BoNT/D constitutes a potential treatment alternative for BoNT/A & B non-responders., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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