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靶向衰老机制的治疗药物临床前开发的障碍

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms.

作者信息

Burd Christin E, Gill Matthew S, Niedernhofer Laura J, Robbins Paul D, Austad Steven N, Barzilai Nir, Kirkland James L

机构信息

Department of Molecular Genetics and.

Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus.

出版信息

J Gerontol A Biol Sci Med Sci. 2016 Nov;71(11):1388-1394. doi: 10.1093/gerona/glw112. Epub 2016 Aug 16.

Abstract

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline.

摘要

随着基础科学研究的进展,与年龄相关衰退的基本机制正得到越来越深入和详细的描述。尽管这些研究已确定了可延长模式生物寿命的新药物靶点和化合物,但针对衰老过程的治疗方法的临床试验仍然很少。衰老研究的进展受到基础科学发现转化为临床应用相关障碍的阻碍。本报告总结了2014年老年科学网络务虚会上的讨论内容,这些讨论聚焦于确定当前阻碍针对基本衰老过程的药物临床前开发的障碍。从这些讨论中可以明显看出,衰老研究人员对理想的临床前研发流程有不同的看法。为了开创一条清晰且连贯的前进道路,必须首先解决几个有争议的领域并开发新工具。在此,我们聚焦于临床前药物开发中的五个关键问题(药物发现、先导化合物开发、转化型临床前生物标志物、资金以及研究人员与临床医生之间的整合),扩展了在老年科学务虚会上的讨论内容,并提出了进一步研究的领域。通过将这些发现提请衰老研究界关注,我们希望为协调一致的临床前药物开发流程奠定基础。

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