PDF(Pubmed)
Abstract：
Hereditary amyloid transthyretin (ATTRv) amyloidosis is a devastating hereditary multisystemic disease affecting predominantly the peripheral and autonomic nervous systems and the heart. ATTRv is caused by mutations in the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. If untreated, it is associated with a fatal outcome 10-12 years after disease onset. Different treatments are available for patients with ATTRv polyneuropathy. Tafamidis 20 mg is approved in Europe since 2011 for early stages of ATTRv polyneuropathy (stage I - able to walk without support) and it is recommended as first-line therapy in these patients. Tafamidis is a TTR stabilizer that selectively binds to TTR and kinetically stabilizes both wild-type native TTR and mutant TTR. Consequently, it has the potential to prevent the amyloidogenic cascade initiated by TTR tetramer dissociation into its monomers and subsequent misfolding and aggregation. Tafamidis is an oral drug, taken once per day, with proved efficacy, safety and tolerability in ATTRv-PN patients as demonstrated in different clinical trials and open-label extension studies as well in clinical practice setting with around 10 years of experience. Tafamidis treatment started in the earliest stages of the disease is associated with better neurological outcomes. A multidisciplinary approach in referral centres is also fundamental for monitoring patients to assess individual response to treatment.
摘要：
遗传性淀粉样蛋白转甲状腺素（ATTRv）淀粉样变性是一种破坏性的遗传性多系统疾病，主要影响外周和自主神经系统以及心脏。ATTRv是由转甲状腺素蛋白（TTR）基因突变引起的，导致淀粉样原纤维在包括周围神经系统在内的多个器官中的细胞外沉积。如果未经治疗,它与疾病发作后10-12年的致命结局有关.ATTRv多发性神经病患者有不同的治疗方法。自2011年以来，Tafamidis20mg在欧洲被批准用于ATTRv多发性神经病的早期阶段（I期-无需支撑即可行走），并建议将其作为这些患者的一线治疗。Tafamidis是选择性结合TTR并在动力学上稳定野生型天然TTR和突变型TTR的TTR稳定剂。因此,它具有防止由TTR四聚体解离成其单体以及随后的错误折叠和聚集引发的淀粉样级联的潜力。Tafamidis是一种口服药物，每天服用一次，具有证明的功效，ATTRv-PN患者的安全性和耐受性在不同的临床试验和开放标签延伸研究以及临床实践中都有大约10年的经验。在疾病的最早阶段开始的Tafamidis治疗与更好的神经系统预后相关。转诊中心的多学科方法对于监测患者以评估个人对治疗的反应也至关重要。
