阿基勒斯肌病的治疗选择:临床前研究的范围审查
Nathanael Opoku Agyeman-Prempeh1,2,3, Huub Maas2,4, George L Burchell4
1University of Amsterdam, Amsterdam, Netherlands.
PeerJ
|January 14, 2025
概括
在临床前研究中,创新的阿基里斯肌病 (AT) 治疗方法显示出前景,改善肌特性. 然而,研究质量不佳和模型的局限性阻碍了临床翻译.
科学领域:
- 生物医学工程 生物医学工程
- 再生医学是一种再生医学.
- 整形外科 整形外科 整形外科
背景情况:
- 阿基里斯肌病 (AT) 由于有效治疗方法有限以及其退行性质,提出了管理挑战.
- 创新疗法至关重要,临床前研究对于理解分子效应和毒性至关重要.
- 在AT临床前研究中缺乏对基本分子机制的全面,质量评估的审查.
研究的目的:
- 总结和评估关于AT治疗的体外和体内动物研究.
- 评估这些治疗对肌特性 (生物力学,组织学,生物化学) 的影响.
- 提供包含的动物研究的质量评估,并指导未来的临床前研究.
主要方法:
- 对PubMed,Embase,Web of Science和Cochrane图书馆研究的范围审查,截至2023年5月4日.
- 包括化学或机械诱导的AT模型 (体外和体内) 报告相关结果的研究.
- 数据提取和归纳分类,并使用实验室动物实验系统审查中心的工具进行偏差风险评估.
主要成果:
- 98项研究调查了65种治疗方法;80%的人报告了阿基里斯肌的显著改善.
- 关键的改进包括增强的最大负载和刚性,恢复的纤维结构和减少的炎症.
- 治疗后I型原蛋白增加,III型原蛋白减少,炎症细胞减少;然而,65.4%-92.5%的研究对偏差高风险存在不确定性.
结论:
- 对AT治疗存在有希望的临床前结果,但临床转化缓慢.
- 动物模型的面部有效性差,异质的诱导方法和研究质量低下阻碍了进展.
- 标准化的临床前模型,改进的报告和最小化的偏见对于成功的AT疗法的临床转化至关重要.
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