Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
Pulm Circ. 2014 Mar;4(1):2-9. doi: 10.1086/674886.
The failure to translate positive results from preclinical studies into new clinical therapies is a major problem throughout medical research. Specifically, in pulmonary hypertension, numerous research studies have shown beneficial effects of new therapies in experimental models, but these have largely failed to translate into clinical benefit in human trials. This is undoubtedly due, at least in part, to inadequacies of the models, but while monogenic animal models will never fully recapitulate human disease, they do still provide the best platform on which to test novel therapeutic agents. In the postgenomic era, there is emphasis on a greater understanding of disease pathogenesis, which has subsequently led to the development of both new targets and new models in which to test them. The evolution of new technologies means that we are now better equipped to phenotype these models, but the level of detail provided varies dramatically throughout the literature. However, subtle variances in experimental methods can make comparing data/findings between research laboratories difficult and are a possible contributing factor to variance between preclinical and clinical data. The aim of this report was to capture information on current practice for use of the growing array of animal models, to help movement toward developing guidelines and standards for the "best" use of animal models of pulmonary hypertension.
未能将临床前研究的阳性结果转化为新的临床治疗方法，是整个医学研究中的一个主要问题。具体来说，在肺动脉高压中，许多研究表明新疗法在实验模型中具有有益效果，但在人体试验中这些疗法在很大程度上未能转化为临床益处。这无疑至少部分归因于模型的不足，但尽管单基因动物模型永远无法完全再现人类疾病，但它们仍然是测试新型治疗药物的最佳平台。在后基因组时代，人们更加重视对疾病发病机制的深入了解，这继而导致了新靶点和新模型的开发，以便对它们进行测试。新技术的发展意味着我们现在能够更好地对这些模型进行表型分析，但文献中提供的细节水平差异很大。然而，实验方法的细微差异使得比较研究实验室之间的数据/发现变得困难，并且可能是导致临床前和临床数据之间差异的一个因素。本报告的目的是收集有关当前动物模型使用情况的信息，以帮助制定指导方针和标准，以“最佳”利用肺动脉高压动物模型。
