Botulinum neurotoxin serotypes A and C do not affect motor units survival in humans: an electrophysiological study by motor units counting.

Abstract

OBJECTIVES:

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.

• Authors: Roberto Eleopra, Valeria Tugnoli, Rocco Quatrale, Ernesto Gastaldo, Ornella Rossetto, Domenico De Grandis, Cesare Montecucco
• Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology (Clin Neurophysiol) Vol. 113 Issue 8 Pg. 1258-64 (Aug 2002) ISSN: 1388-2457 [Print] Netherlands
• PMID: 12140005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuromuscular Agents
• Botulinum Toxins
• Botulinum Toxins, Type A
• botulinum toxin type C

Topics

• Animals
• Botulinum Toxins (administration & dosage, pharmacology, therapeutic use)
• Botulinum Toxins, Type A (administration & dosage, pharmacology, therapeutic use)
• Cell Count
• Cell Survival
• Cells, Cultured
• Dystonia (drug therapy)
• Electric Stimulation
• Electrophysiology
• Hemifacial Spasm (drug therapy)
• Humans
• Kinetics
• Male
• Mice
• Motor Neurons (physiology)
• Neuromuscular Agents (pharmacokinetics)
• Neuromuscular Junction (physiology)
• Phrenic Nerve (physiology)