PDF(Pubmed)
Abstract：
Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant, life-threatening genetic disorder caused by a single-nucleotide variant in the transthyretin gene. This mutation leads to the misfolding and deposition of amyloid in various body organs. Both mutant and wild-type transthyretin contribute to the resulting polyneuropathy and cardiomyopathy, leading to significant sensorimotor disturbances and severe cardiac conditions such as heart failure and arrhythmias, thereby impacting quality of life. Despite several treatments, including orthotopic liver transplantation and transthyretin tetramer stabilizers, their limitations persisted until the introduction of RNA interference (RNAi). RNAi, a means to regulate mRNA stability and translation of targeted genes, has brought about significant changes in treatment strategies for ATTR with the introduction of patisiran in 2018. This study reviews patisiran, vutrisiran, inotersen, and eplontersen, developed for the treatment of ATTR. It provides an overview of the clinical trial outcomes, focusing mainly on quality of life, adverse reactions, and the future of RNAi-based therapies.
摘要：
遗传性转甲状腺素蛋白淀粉样变性（ATTR）是常染色体显性，由甲状腺素运载蛋白基因中的单核苷酸变异引起的危及生命的遗传性疾病。这种突变导致淀粉样蛋白在各种身体器官中的错误折叠和沉积。突变型和野生型甲状腺素运载蛋白都有助于导致多发性神经病和心肌病，导致严重的感觉运动障碍和严重的心脏疾病，如心力衰竭和心律失常，从而影响生活质量。尽管有几次治疗，包括原位肝移植和转甲状腺素四聚体稳定剂，直到引入RNA干扰（RNAi），它们的局限性仍然存在。RNAi,调节mRNA稳定性和目标基因翻译的手段，随着2018年patisiran的引入，ATTR的治疗策略发生了重大变化。这项研究回顾了patisiran，vutrisiran,Inotersen,还有Eplontersen,用于治疗ATTR。它提供了临床试验结果的概述，主要关注生活质量，不良反应,以及基于RNAi的疗法的未来。
