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Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients.
- Source :
-
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology [Clin Neurophysiol] 2019 Jun; Vol. 130 (6), pp. 1066-1073. Date of Electronic Publication: 2019 Feb 28. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.<br />Significance: BoNT/D constitutes a potential treatment alternative for BoNT/A & B non-responders.<br /> (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1872-8952
- Volume :
- 130
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 30871800
- Full Text :
- https://doi.org/10.1016/j.clinph.2019.02.007