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

Abstract

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. 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. 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. We conclude that BoNT/C, similarly to BoNT/A, is safe and effective in humans and it could be proposed for a clinical use.