Ikeda Shu-ichi
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine.
Rinsho Shinkeigaku. 2009 Nov;49(11):953-5. doi: 10.5692/clinicalneurol.49.953.
Familial amyloid polyneuropathy (FAP) was long considered to be an incurable disease, but a new therapeutic approach was developed 15 years ago. As the liver produces most of the transthyretin (TTR) in serum, it was assumed that the replacement of a liver expressing an abnormal TTR gene should stop the production of the variant TTR, the serum amyloid precursor in FAP. Until now about 1,500 FAP patients underwent liver transplantation, and the 10-year-survival rate is about 77%. After operation the progression of FAP symptoms certainly stopped, and patients who were in an early stage of the disease and underwent successful operations showed considerable improvement in their quality of life. Electrophysiological study of peripheral nerve function has demonstrated that liver transplantation can halt the progression of peripheral neuropathy in FAP patients, and histopathological regression of amyloid deposits was seen on the patients with long post-transplatation courses. Pharmacological therapies have been considered for FAP patients and among them, diflunisal, one of non-steroidal antiinflammatory drugs, is very promising. TTR tetramer dissociation is an initial step for the process of TTR-derived amyloid fibril formation associated with FAP and diflinisal can inhibit this process by stabilization of the TTR tetramer. Clinical trial of this drug for FAP patients is now going worldwide.
家族性淀粉样多神经病（FAP）长期以来被认为是一种无法治愈的疾病，但15年前开发出了一种新的治疗方法。由于肝脏产生血清中大部分的转甲状腺素蛋白（TTR），因此人们认为替换表达异常TTR基因的肝脏应该会停止变异TTR的产生，而变异TTR是FAP中的血清淀粉样前体。到目前为止，约1500名FAP患者接受了肝移植，10年生存率约为77%。手术后FAP症状的进展肯定停止了，处于疾病早期且手术成功的患者生活质量有了显著改善。对周围神经功能的电生理研究表明，肝移植可以阻止FAP患者周围神经病变的进展，并且在移植后病程较长的患者中观察到淀粉样沉积物的组织病理学消退。FAP患者也考虑过药物治疗，其中非甾体抗炎药双氟尼酸很有前景。TTR四聚体解离是与FAP相关的TTR衍生淀粉样纤维形成过程的第一步，双氟尼酸可以通过稳定TTR四聚体来抑制这一过程。这种药物用于FAP患者的临床试验目前正在全球范围内进行。
