Dose-dependent Effects of Botulinum Toxin Type E in the Mouse Digit Abduction Score Model

Botulinum Toxin Type A (BOTOX^®) is widely used, but its long duration may be unsuitable when a rapid and short-lasting effect is desired. This study aimed to evaluate the dose-dependent effects of botulinum toxin type E (JTM204) in the mouse digit abduction score model and compare its onset and duration with BOTOX^®.

Female Institute of Cancer Research (ICR) mice received intramuscular injections of JTM204 at doses of 18.2, 28.9, 45.5, 72.2, 115.0, or 182.0 U/kg into the right gastrocnemius muscle. Mouse digit abduction score (DAS) responses were scored using a 0-4 scale at multiple time points from 3 to 72 h post-injection. Peak response, duration of effect, and dose dependency were assessed. The highest JTM204 dose was compared with contemporaneously evaluated BOTOX^® data at 24.3 U/kg.

JTM204 produced a rapid, dose-dependent inhibition of digit abduction. Detectable activity was observed by 3 h, with peak effects occurring between 12 and 24 h. The highest dose produced the strongest response, reaching a mean peak DAS of approximately 3.6. DAS values declined markedly by 48 h and returned to baseline by 72 h in all dose groups. Compared with BOTOX^®, JTM204 showed a faster onset and much shorter duration, while Botulinum Toxin Type A peaked later and persisted for up to 14 days.

JTM204 demonstrated rapid-onset, dose-dependent, and fully reversible muscle-weakening activity, supporting its potential as a short-acting botulinum toxin for applications requiring temporary neuromuscular blockade.