转甲状腺素淀粉样蛋白心肌病当前和新兴的治疗选择。

IF 5.1 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Heart Pub Date : 2025-05-27 DOI:10.1136/heartjnl-2024-325184
Giuseppe Vergaro, Yu Fu Ferrari Chen, Adam Ioannou, Giorgia Panichella, Vincenzo Castiglione, Alberto Aimo, Michele Emdin, Marianna Fontana
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引用次数: 0

摘要

转甲状腺素淀粉样变性(ATTR)是一种由TTR蛋白错误折叠和淀粉样蛋白沉积引起的疾病,特别是在心脏和神经系统,导致器官功能障碍。治疗策略的进步已经彻底改变了ATTR淀粉样变的管理。临床实践中可用的治疗方法包括TTR稳定剂(tafamidis和acoramidis),它们可以防止TTR四聚体解离成单体和寡聚体,从而形成淀粉样蛋白原纤维,以及基因沉默疗法(patisiran, intertersen和vutrisiran),它们抑制肝脏合成TTR, TTR是淀粉样蛋白的前体蛋白。处于不同发展阶段的新型治疗策略包括Clustered Regularly Interspaced Short Palindromic Repeats-Cas9基因编辑技术(nexiguran ziclumeran),如果成功,它将提供单剂量治疗的前景,以及单克隆(commitug和ALXN220)和泛淀粉样蛋白抗体(at -02),它们寻求靶向并去除沉积在心肌中的淀粉样蛋白原纤维。淀粉样蛋白去除仍然是一个重要的未满足的临床需求,因此,通过使用抗淀粉样蛋白疗法促进淀粉样蛋白降解和清除的能力将代表着ATTR淀粉样变性治疗的突破性进展。atr特异性疾病修饰疗法的成功已经改变了治疗前景,并将ATTR淀粉样变性从一种进行性和致命性疾病转变为一种可通过高效疾病修饰疗法治疗的疾病。然而,重要的问题仍然存在,包括这些药物的长期安全性,不同作用机制的联合治疗是否具有附加的预后益处,以及如何最好地监测治疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Current and emerging treatment options for transthyretin amyloid cardiomyopathy.

Transthyretin amyloidosis (ATTR) is a condition caused by TTR protein misfolding and amyloid deposition, particularly in the heart and nervous system, leading to organ dysfunction. Advances in therapeutic strategies have revolutionised the management of ATTR amyloidosis. Treatments available in clinical practice include TTR stabilisers (tafamidis and acoramidis), which prevent the dissociation of TTR tetramer into monomers and oligomers that subsequently form amyloid fibrils, and gene-silencing therapies (patisiran, inotersen and vutrisiran), which suppress the hepatic synthesis of TTR, which is the amyloid precursor protein. Novel treatment strategies that are at various stages of development include Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 gene-editing technology (nexiguran ziclumeran), which, if successful, offers the prospect of a single-dose treatment, and monoclonal (cormitug and ALXN220) and pan-amyloid antibodies (AT-02) that seek to target and remove amyloid fibrils that have deposited in the myocardium. Amyloid removal remains a significant unmet clinical need, and hence, the ability to promote amyloid degradation and clearance through the use of antiamyloid therapies would represent a groundbreaking advancement in the treatment of ATTR amyloidosis. The success of ATTR-specific disease-modifying therapies has already altered the treatment landscape and changed the perception of ATTR amyloidosis from a progressive and fatal disease to one that is treatable through the availability of highly effective disease-modifying therapies. However, important questions remain, including the long-term safety of these drugs, whether combining therapies with different mechanisms of action has an additive prognostic benefit and how best to monitor the treatment response.

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来源期刊
Heart
Heart 医学-心血管系统
CiteScore
10.30
自引率
5.30%
发文量
320
审稿时长
3-6 weeks
期刊介绍: Heart is an international peer reviewed journal that keeps cardiologists up to date with important research advances in cardiovascular disease. New scientific developments are highlighted in editorials and put in context with concise review articles. There is one free Editor’s Choice article in each issue, with open access options available to authors for all articles. Education in Heart articles provide a comprehensive, continuously updated, cardiology curriculum.
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