Du Xiao-Jun, Hewitson Tim D, Nguyen My-Nhan, Samuel Chrishan S
Baker IDI Heart and Diabetes Institute, Monash University.
Circ J. 2014;78(3):542-52. doi: 10.1253/circj.cj-14-0014. Epub 2014 Jan 23.
Over the past few decades, research on the peptide hormone, relaxin, has significantly improved our understanding of its biological actions under physiological and diseased conditions. This has facilitated the conducting of clinical trials to explore the use of serelaxin (human recombinant relaxin). Acute heart failure (AHF) is a very difficult to treat clinical entity, with limited success so far in developing new drugs to combat it. A recent phase-III RELAX-AHF trial using serelaxin therapy given during hospitalization revealed acute (ameliorated dyspnea) and chronic (improved 180-day survival) effects. Although these findings support a substantial improvement by serelaxin therapy over currently available therapies for AHF, they also raise key questions and stimulate new hypotheses. To facilitate the development of serelaxin as a new drug for heart disease, joint efforts of clinicians, research scientists and pharmacological industries are necessary to study these questions and hypotheses. In this review, after providing a brief summary of clinical findings and the pathophysiology of AHF, we present a working hypothesis of the mechanisms responsible for the observed efficacy of serelaxin in AHF patients. The existing clinical and preclinical data supporting our hypotheses are summarized and discussed. The development of serelaxin as a drug provides an excellent example of the bilateral nature of translational research.
在过去几十年里，对肽类激素松弛素的研究极大地增进了我们对其在生理和疾病状态下生物学作用的理解。这推动了探索重组人松弛素（serelaxin）用途的临床试验开展。急性心力衰竭（AHF）是一种极难治疗的临床病症，迄今为止在开发治疗该病的新药方面成效有限。最近一项在住院期间使用serelaxin治疗的III期RELAX - AHF试验显示出急性（缓解呼吸困难）和慢性（改善180天生存率）效果。尽管这些发现表明serelaxin治疗比目前可用的AHF治疗方法有显著改善，但它们也提出了关键问题并激发了新的假设。为推动serelaxin作为心脏病新药的研发，临床医生、科研人员和制药行业需要共同努力来研究这些问题和假设。在本综述中，在简要总结临床发现和AHF的病理生理学之后，我们提出了一个关于serelaxin在AHF患者中观察到的疗效机制的工作假设。对支持我们假设的现有临床和临床前数据进行了总结和讨论。serelaxin作为一种药物的研发为转化研究的双向性提供了一个很好的例子。
