Preclinical Evaluation of Botulinum Toxin Type E (TrenibotulinumtoxinE) Using the Mouse Digit Abduction Score (DAS) Assay.

IF 4 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Toxins Pub Date : 2025-05-06 DOI:10.3390/toxins17050230

Gregory S Nicholson, David Canty, Annemarie Southern, Kevin Whelan, Amy D Brideau-Andersen, Ron S Broide

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引用次数: 0

Abstract

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24-27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule.

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用小鼠手指外展评分（DAS）法评价E型肉毒毒素（TrenibotulinumtoxinE）的临床前评价。

treniboulinumtoxine （trenibotE）是一种E血清型肉毒杆菌神经毒素（BoNT/E），正在开发用于临床，可以填补寻求神经毒素治疗的患者的独特治疗空白，其起效快，持续时间短。本临床前研究利用小鼠手指外展评分（DAS）测定表征了trenibotE的药理活性。比较分析还进行了trenibotE和等有效剂量的肉毒杆菌神经毒素血清型A （BoNT/A）肉毒杆菌毒素A （onabotA）。TrenibotE显示出DAS峰值和作用时间的剂量依赖性增加。在该试验中，onabotA和trenibotE在大约相同有效剂量下的比较显示，trenibotE起效更快（trenibotE在注射后6小时产生显著更大的效果），达到效果峰值的时间更短（24-27小时vs. 2天），总体反应持续时间更短（3天vs. 14天）。在临床前试验中观察到的trenibotE的独特时间特征和与onabotA的药理差异支持了该分子的临床开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxins TOXICOLOGY-

CiteScore

7.50

自引率

16.70%

发文量

765

审稿时长

16.24 days

期刊介绍： Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.