Schwartzlow Coreen, Kazamel Mohamed
Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL.
J Clin Neuromuscul Dis. 2020 Mar;21(3):144-156. doi: 10.1097/CND.0000000000000270.
Hereditary transthyretin amyloidosis, once a rare progressive neuropathy and/or cardiomyopathy, is now recognized with increasing worldwide frequency, various phenotypes, and over 130 gene mutations identified to date. This inherited disorder develops as a result of mutated transthyretin amyloid aggregation and systematic deposition throughout the body. With increasing knowledge about the pathophysiology of this disease, new disease-modifying therapies are being developed. In addition to slowing progression, these new agents were found to improve quality of life and reduce the severity of neuropathic symptoms. Two new gene-modifying therapies recently received Food and Drug Administration approval following the positive results from phase III trials. These include an antisense oligonucleotide, inotersen, and small interfering RNA, patisiran, which were reported to reduce the production of transthyretin and had promising safety profiles. Additional novel therapies are being explored with hopes to prolong survival. Therefore, early diagnosis of this treatable disorder has become increasingly important in clinical practice.
遗传性转甲状腺素蛋白淀粉样变性病，曾是一种罕见的进行性神经病变和/或心肌病，如今在全球范围内的发病率日益增加，具有多种表型，且迄今已鉴定出130多种基因突变。这种遗传性疾病是由于突变的转甲状腺素蛋白淀粉样聚集并在全身系统性沉积而发展起来的。随着对该疾病病理生理学的了解不断增加，正在开发新的疾病修饰疗法。除了减缓疾病进展外，这些新药物还被发现可改善生活质量并减轻神经病变症状的严重程度。在III期试验取得阳性结果后，两种新的基因修饰疗法最近获得了美国食品药品监督管理局的批准。其中包括反义寡核苷酸inotersen和小干扰RNA（siRNA）patisiran，据报道它们可减少转甲状腺素蛋白的产生，并且具有良好的安全性。正在探索其他新型疗法，以期延长生存期。因此，在临床实践中对这种可治疗疾病进行早期诊断变得越来越重要。
