Paton D M
Professor Emeritus of Pharmacology, University of Auckland, Auckland, New Zealand; Professor Emeritus of Oral Biology, University of Alberta, Edmonton, Alberta, Canada.
Drugs Today (Barc). 2019 Dec;55(12):727-734. doi: 10.1358/dot.2019.55.12.3078389.
Plasma protein transthyretin (TTR) can undergo conformational change resulting in the formation of amyloid fibrils that can then cause amyloidosis. This can occur spontaneously in individuals over the age of 70-80 resulting in wild-type transthyretin amyloidosis (ATTR) (with cardiomyopathy). This then progresses to fatal cardiac failure. TTR can also undergo conformational change in individuals who have a genetic abnormality in the structure of TTR resulting in hereditary ATTR amyloidosis. This is usually first manifested as polyneuropathy but can progress to cardiomyopathy with time. Until recently, there has been no specific treatment for these conditions. However, a detailed search for compounds that stabilize TTR resulted in the discovery of tafamidis. This compound stabilizes TTR and has been found to significantly reduce the progression of both wild-type ATTR amyloidosis and hereditary ATTR amyloidosis.
血浆蛋白转甲状腺素蛋白（TTR）可发生构象变化，导致淀粉样原纤维形成，进而引发淀粉样变性。这种情况可在70至80岁以上的个体中自发发生，导致野生型转甲状腺素蛋白淀粉样变性（ATTR）（伴有心肌病）。随后会发展为致命的心力衰竭。TTR在转甲状腺素蛋白结构存在基因异常的个体中也会发生构象变化，导致遗传性ATTR淀粉样变性。这通常首先表现为多发性神经病，但随着时间的推移可能会发展为心肌病。直到最近，这些病症都没有特效治疗方法。然而，对稳定TTR的化合物进行的详细研究发现了他氟米特。这种化合物可稳定TTR，并已发现能显著减缓野生型ATTR淀粉样变性和遗传性ATTR淀粉样变性的进展。
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