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. 2022 Jun;10(3):e00955.
doi: 10.1002/prp2.955.

Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins

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Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins

Wu-Chao Liu et al. Pharmacol Res Perspect. 2022 Jun.

Abstract

Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.

Keywords: botulinum toxin A; chinbotulinumtoxin A; complex proteins; muscle strength.

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Figures

FIGURE 1
FIGURE 1
Dynamic paralytic effects of different doses of A/Chin on the gastrocnemius muscle strength of rats. **p < .01 and ***p < .001 for 0.01 U A/Chin versus the NS group. ## p < .01 and ### p < .001 for 4 U A/Chin versus the NS group. All data points represent mean ± SE
FIGURE 2
FIGURE 2
Right gastrocnemius muscle strength of rats after different doses of BTX‐As injection at three key timepoints. *p < .05, **p < .01 and ***p < .001 versus the NS group. # p < .05, ## p < .01 and ### p < .001 versus the 0.01 U A/Chin group. All columns represent mean ± SE
FIGURE 3
FIGURE 3
Hematoxylin–eosin staining of gastrocnemius muscle after injection of 2 U A/Chin and other BTX‐As for 28 days

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