Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild-type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin-3-gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.

中文翻译：

---

运甲状腺素蛋白淀粉样变性的新兴疗法-多年停滞后的新希望浪潮？

运甲状腺素蛋白淀粉样变性病（ATTR）是一种罕见但尚未被充分诊断的疾病，其特征在于由于运甲状腺素蛋白折叠错误而导致神经和心脏功能的逐步损害。尽管进行了许多努力，例如采用了原位肝移植，但由于缺乏特异性疗法，过去几十年来，变异型和野生型ATTR患者的毁灭性预后均未发生变化。幸运的是，近年来出现了有前途的靶向疗法，其目的是干扰在ATTR进展的级联反应的各个阶段错折叠的甲状腺素（TTR）的沉积。这些包括TTR四聚体稳定剂（他法米地，地氟尼松，表没食子儿茶素-3-没食子酸酯），TTR沉默子（伊诺特森，patisiran）和原纤维破坏者（单克隆抗体，强力霉素和牛磺去氧胆酸）。在这篇综述中，我们根据迄今为止进行的所有临床试验解释了它们的作用机理，分析了它们对神经和心脏功能的功效，并讨论了它们的临床适用性。最终提供了对该领域未来临床研究的建议。