Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients.
Clin Neurophysiol
; 130(6): 1066-1073, 2019 06.
Article
in En
| MEDLINE
| ID: mdl-30871800
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 (nâ¯=â¯30) of human volunteers. Their compound muscle action potentials were measured 11 times by electroneurography within 220â¯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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Botulinum Toxins
/
Muscle, Skeletal
/
Botulinum Toxins, Type A
/
Neuromuscular Agents
Limits:
Adult
/
Animals
/
Humans
/
Male
Language:
En
Journal:
Clin Neurophysiol
Journal subject:
NEUROLOGIA
/
PSICOFISIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Germany