Suhr Ole B, Gustavsson Sandra, Heldestad Victoria, Hörnsten Rolf, Lindqvist Per, Nordh Erik, Wiklund Urban
Department of Public Health and Clinical Medicine,
Department of Pharmacology and Clinical Neuroscience.
Degener Neurol Neuromuscul Dis. 2012 Aug 28;2:93-106. doi: 10.2147/DNND.S24652. eCollection 2012.
Over the last decade, new medical treatment modalities have emerged based on increased insights into amyloid formation. With the increased possibilities for treatment of amyloidosis caused by transthyretin (TTR) amyloid deposits comes the need for diagnostic procedures for early diagnosis and better tools to follow disease progression. This is of particular importance in clinical trials evaluating the efficacy of new treatments. Until recently, the treatment of TTR amyloidosis (ATTR) was based solely on liver transplantation, a procedure that has halted disease progression in many patients. Liver transplantation has been especially effective in patients under the age of 50 years carrying the TTR V30M mutation, whereas the outcome of the procedure has been variable for others, particularly elderly male patients and those carrying a non-V30M mutation. This review concentrates on new insights derived from our center's experience with liver transplantation, how to implement this experience in evaluation of new treatment modalities for ATTR, and how to facilitate early diagnosis of neuropathy with easily available diagnostic tools. Attention has focused on manifestations of the disease that involve the heart and the peripheral nervous system; change in peripheral nerve function has been the primary endpoint in two controlled clinical trials, one finished and one ongoing. New insights into the amyloid formation process and the lessons learned from liver transplantation give the opportunity to design potentially effective treatment modalities for ATTR. It appears reasonable to suspect that a combination of different treatment modalities may be required to treat the disease, and that different treatment regimes will be designed according to the phenotype of the disease. For the patients and their relatives there is now a solid foundation for optimism, with prospects of several effective medical treatment possibilities within the coming decade.
在过去十年中，随着对淀粉样蛋白形成的深入了解，出现了新的医学治疗方式。随着治疗由转甲状腺素蛋白（TTR）淀粉样蛋白沉积引起的淀粉样变性的可能性增加，对早期诊断的诊断程序以及跟踪疾病进展的更好工具的需求也随之而来。这在评估新治疗方法疗效的临床试验中尤为重要。直到最近，TTR淀粉样变性（ATTR）的治疗仅基于肝移植，这一手术已使许多患者的疾病进展停止。肝移植在携带TTR VV30M突变的50岁以下患者中尤其有效，而对于其他患者，尤其是老年男性患者和携带非V30M突变的患者，该手术的结果则各不相同。本综述集中于我们中心肝移植经验的新见解、如何将这一经验应用于评估ATTR的新治疗方式，以及如何使用易于获得的诊断工具促进神经病变的早期诊断。重点关注了该疾病涉及心脏和周围神经系统的表现；周围神经功能的变化一直是两项对照临床试验的主要终点，一项已经完成，另一项正在进行。对淀粉样蛋白形成过程的新见解以及从肝移植中学到的经验教训为设计可能有效的ATTR治疗方式提供了机会。合理推测可能需要结合不同的治疗方式来治疗该疾病，并且将根据疾病的表型设计不同的治疗方案。对于患者及其亲属来说，现在有了坚实的乐观基础，在未来十年内有望出现几种有效的医学治疗方法。
