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从相关动物模型到患者的整个过程中,使用实用生物标志物进行纤维肌痛的药物发现与开发。

Drug discovery and development for fibromyalgia using practical biomarkers throughout the process from relevant animal models to patients.

作者信息

Nagakura Yukinori, Tozaki-Saitoh Hidetoshi, Takeda Hiroshi

机构信息

School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan.

出版信息

Expert Opin Drug Discov. 2023 May;18(5):539-549. doi: 10.1080/17460441.2023.2202908. Epub 2023 Apr 13.

Abstract

INTRODUCTION

Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain and complex comorbidities with a high unmet medical need. Given few past successes in the launch of analgesics with new mechanisms, the implementation of practical biomarkers for drug discovery and development would be necessary to rationally create innovative drugs for chronic pain conditions, including FM.

AREAS COVERED

This review surveys the evidence on pathophysiology of FM and the findings regarding the pathophysiology-associated practical biomarker candidates in body fluids (e.g. blood) from the studies in FM patients. This review also summarizes the most commonly used animal models simulating key aspects of clinical FM features. Finally, a strategy for rationally creating innovative drugs for FM is discussed.

EXPERT OPINION

Drug discovery and development for FM targeting immune dysregulation/inflammation would be a viable strategy based on the availability of the pathophysiology-associated practical biomarkers (e.g. serum interleukins), which monitor the efficacy of interventions and/or identify responders based on the matching pathophysiology throughout the process from animal models to patients. This strategy could lead to a breakthrough in the development of drugs for FM, a chronic pain condition.

摘要

引言

纤维肌痛(FM)是一种慢性疼痛疾病,其特征为广泛疼痛和复杂的合并症,存在大量未满足的医疗需求。鉴于过去新型作用机制镇痛药的推出鲜有成功案例,为合理研发针对包括FM在内的慢性疼痛疾病的创新药物,有必要实施用于药物研发的实用生物标志物。

涵盖领域

本综述调查了FM病理生理学的证据以及FM患者研究中体液(如血液)中与病理生理学相关的实用生物标志物候选物的研究结果。本综述还总结了模拟临床FM特征关键方面的最常用动物模型。最后,讨论了合理研发FM创新药物的策略。

专家观点

基于与病理生理学相关的实用生物标志物(如血清白细胞介素)的可用性,针对免疫失调/炎症的FM药物研发将是一种可行的策略,这些生物标志物可在从动物模型到患者的整个过程中监测干预效果和/或根据匹配的病理生理学识别反应者。这一策略可能会在FM这种慢性疼痛疾病的药物研发方面取得突破。

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