Biomedical Sciences Research Center Alexander Fleming,Institute of Immunology, Vari-Athens, Greece.
Ann Rheum Dis. 2011 Aug;70(8):1357-62. doi: 10.1136/ard.2010.148551. Epub 2011 May 30.
The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in 'omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology.
新型类风湿关节炎（RA）治疗方法的开发需要临床观察和动物模型研究之间的相互作用。鉴于 RA 的复杂分子发病机制和高度异质的临床特征，迫切需要剖析其多因素性质，并提出新的预防、早期和治疗策略。动物模型研究为 RA 的病理生理学和病因学提供了新的知识，并为创新药物的开发提供了非常成功的范例。最近的重点已经转向发现新的生物标志物，重点是人类 RA 的无症状和早期阶段，并致力于解决不同疾病变异背后的病理生理机制和干预措施的后续疗效。RA 发病机制中当前范式的转变也导致对新型（包括人源化）动物模型的需求增加。因此，迫切需要将人类和动物模型的知识结合起来，最终创建一个全面的“发病机制图谱”，以指导现有和新型动物模型与它们模拟的疾病子集的匹配。这需要在基因型、表型和生物标志物水平上对所有模型进行充分和标准化的描述，利用“组学”分析和计算生物学以及最先进的生物成像技术的最新技术发展。为了管理积累的大量数据并提高社区对创新型动物模型研究的认识和支持，有必要进行有效的信息和资源整合以及推广。
