Botulinum neurotoxin serotypes A and C do not affect motor units survival in humans: an electrophysiological study by motor units counting.
OBJECTIVE
Botulinum neurotoxin serotype A (BoNT/A) is a valid therapy for dystonia but repeated BoNT/A injections may induce a clinical immuno-resistance that could be overcome by using other BoNT serotypes. In vitro experiments and our preliminary investigations in vivo, indicate that botulinum neurotoxin serotype C (BoNT/C) could be an effective alternative to BoNT/A. Moreover, in cultured neurons 'in vitro' BoNT/C has been reported to be more toxic than BoNT/A.


METHODS
To verify this possibility, we compare the effect of BoNT/C and BoNT/A on the motor units count in humans by using the electrophysiological motor unit number estimation (MUNE) technique ('multiple point nerve stimulation'). Preliminarily, BoNT/C and BoNT/A dosage was calibrated in a mouse hemidiaphragm neuromuscular junction preparation. Subsequently, 8 volunteers were treated with 3IU of BoNT/C in the extensor digitorum brevis muscle of one foot and 3IU of BoNT/A in the contralateral one. Other 4 subjects were similarly injected at higher doses (10IU of BoNT/C or BoNT/A) to detect a possible dose-toxic effect.


RESULTS
In both groups, no statistically significant variations in MUNE counting or single motor unit potential size were detected after 4 months from injections, when it was evident a recovery from the BoNTs blockade.


CONCLUSIONS
We conclude that BoNT/C, similarly to BoNT/A, is safe and effective in humans and it could be proposed for a clinical use.
Department of Clinical Neuroscience, Neurology Section, S.Anna University Hospital, corso Giovecca 203, Ferrara, Italy. releopra@global.it
Roberto
R
Eleopra
Valeria
V
Tugnoli
Rocco
R
Quatrale
Ernesto
E
Gastaldo
Ornella
O
Rossetto
Domenico
D
De Grandis
Cesare
C
Montecucco
D000818:Animals; D001905:Botulinum Toxins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D004421:Dystonia / Q000188:drug therapy; D004558:Electric Stimulation; D004594:Electrophysiology; D019569:Hemifacial Spasm / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009465:Neuromuscular Agents / Q000493:pharmacokinetics*; D009469:Neuromuscular Junction / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology
D009465:Neuromuscular Agents; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; C096324:botulinum toxin type C