Evolving landscape in the management of transthyretin amyloidosis.
Evolving landscape in the management of transthyretin amyloidosis.
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DOI：
10.3109/07853890.2015.1068949
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发表时间：
2015
影响因子：
4.4
通讯作者：
Suhr OB
中科院分区：
文献类型：
--
作者：
Hawkins PN;Ando Y;Dispenzeri A;Gonzalez-Duarte A;Adams D;Suhr OB
转甲状腺素(Transhyretin，TTR)淀粉样变性是一种多系统、多基因的疾病，其原因是不溶的ATTR淀粉样纤维沉积在各种器官和组织中。虽然被认为是罕见的，但这种严重疾病的流行率可能被低估了，因为症状可能是非特异性的，诊断在很大程度上依赖于组织活检中的淀粉样蛋白检测。尽管晚期疾病患者的治疗选择有限，但治疗是以涉及哪些组织/器官为指导的。事实上，在有明显神经缺陷或心脏受累的患者中，肝移植治疗伴多神经病的家族性ATTR淀粉样变性的热情受到了不良结果的影响。因此，对新疗法的医学需求仍然没有得到满足。在一些伴有多发性神经病的ATTR淀粉样变性患者中，TTR稳定剂他法米司和二氟尼柳延缓了疾病的进展，多西环素和牛磺酸熊去氧胆酸对淀粉样蛋白溶解的假设协同作用正在研究中。另一种治疗方法是减少淀粉样蛋白TTR的产生。ISIS-TTRRx是一种基于反义寡核苷酸的研究药物，Patisiran和Revusiran是一种以肝脏为靶点的研究RNA干扰疗法，使用ISIS-TTRRx可以显著降低血浆TTR浓度。ATTR淀粉样变性不断发展的治疗格局为这种衰弱疾病患者的临床结果带来了进一步改善的希望。
Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease.