Emerging concepts and challenges in the development of disease-modifying osteoarthritis drugs - a more refined perspective.

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Zsuzsa Jenei-Lanzl, Svenja Maurer, Rolf E Brenner, Frank Zaucke, Michael Fuchs, Jana Riegger
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引用次数: 0

Abstract

Osteoarthritis (OA) is the most common joint disease worldwide. Despite significant efforts byresearchers, no disease-modifying osteoarthritis drugs (DMOADs) have been approved yet. This review compares preclinical and clinical studies of promising therapeutic approaches to gain insights into the potential reasons for their failure in clinical trials. For this purpose, prime examples of different therapeutic groups, including the antioxidant NAC, senotherapeutic UBX0101, anti-inflammatory drug Anakinra®, Wnt inhibitor Lorecevivint®, chondroanabolic growth factor Sprifermin™, and various protease inhibitors, are discussed in detail. The limitations of commonly used OA animal models are elaborated to understand this failure better. Moreover, this review addresses the challenges of patient stratification into different endotypes and phenotypes, the consideration of subgrouping in clinical trials, and the lack of suitable clinical outcome parameters. In summary, this review highlights potential reasons for the high failure rate of DMOADs in clinical trials and outlines key points for future improvement.

在改善疾病的骨关节炎药物发展的新兴概念和挑战-一个更精细的观点。
骨关节炎(OA)是世界上最常见的关节疾病。尽管研究人员做出了巨大的努力,但目前还没有一种改善疾病的骨关节炎药物(DMOADs)获得批准。这篇综述比较了有前途的治疗方法的临床前和临床研究,以深入了解它们在临床试验中失败的潜在原因。为此,本文详细讨论了不同治疗组的主要例子,包括抗氧化剂NAC、老年治疗药物UBX0101、抗炎药Anakinra®、Wnt抑制剂Lorecevivint®、软骨合成代谢生长因子Sprifermin™和各种蛋白酶抑制剂。本文阐述了常用OA动物模型的局限性,以便更好地理解这种失败。此外,这篇综述解决了将患者分层为不同内型和表型的挑战,在临床试验中考虑亚组,以及缺乏合适的临床结果参数。总之,本综述强调了dmoad在临床试验中失败率高的潜在原因,并概述了未来改进的关键点。
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
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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