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从基础研究到临床应用:治疗脊髓损伤,是否存在“翻译丢失”?

From bench to beside to cure spinal cord injury: lost in translation?

机构信息

Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.

出版信息

Int Rev Neurobiol. 2012;106:173-96. doi: 10.1016/B978-0-12-407178-0.00008-9.

Abstract

Despite intense efforts to overcome the inhospitable milieu for axonal regeneration within the damaged spinal cord an evidence-based repair strategy promoting relevant functional improvement is still not available for spinal cord injured individuals. Nevertheless, several preclinical axonal regenerative strategies were developed all the way to phase I/II clinical trials, which have recently been terminated. The aim of this chapter is to critically review translated preclinical treatment strategies with respect to their conformity with previously published guidelines and requirements for preclinical studies leading to clinical trials in human subjects with spinal cord injury (SCI). Cell-based strategies (macrophage and embryonic stem cell grafting) and the administration of C3 transferase inhibitors and anti-Nogo-A antibodies were investigated. Overall, these four approaches comply with preclinical quality standards to varying degree. For future preclinical analyses, several additive components such as defined criteria for robustness of observed effects, a clear confirmation of underlying structural mechanisms, and the implementation of appropriate preclinical rehab approaches should be considered in order to increase the quality and consequently the likelihood of respective therapeutic strategies to succeed in human individuals suffering from SCI.

摘要

尽管人们付出了巨大努力来克服受损脊髓中轴突再生的不利环境,但仍没有一种基于证据的修复策略可以促进脊髓损伤患者的相关功能改善。然而,一些临床前轴突再生策略已经发展到了 I/II 期临床试验阶段,但最近这些试验都已终止。本章的目的是批判性地回顾已翻译的临床前治疗策略,评估它们与先前发表的有关临床前研究指南和要求的一致性,这些指南和要求旨在为脊髓损伤(SCI)患者的临床试验提供依据。研究的治疗策略包括细胞策略(巨噬细胞和胚胎干细胞移植)以及 C3 转移酶抑制剂和抗 Nogo-A 抗体的给药。总体而言,这四种方法在不同程度上符合临床前质量标准。对于未来的临床前分析,应考虑增加一些附加成分,如对观察到的效果的稳健性的明确标准、对潜在结构机制的明确确认,以及实施适当的临床前康复方法,以提高相应治疗策略在人类 SCI 患者中的质量和成功率。

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