Antibody Immunotherapy for Systemic and Local Amyloidosis

淀粉样变性是一组罕见但非常严重的疾病，通常是由人体自身蛋白质引起的致命疾病。通常情况下，蛋白质在生产后的不同时间被安全破坏或回收，并被新产生的分子所取代，以发挥其功能。然而，大约有30种不同的人类蛋白质倾向于表现不同。这些蛋白质不是简单安全地被破坏和替换，而是聚集在一起形成长串，形成微小的线状纤维，称为淀粉样原纤维。不可思议的是，由于一些尚不清楚的原因，淀粉样蛋白原纤维并没有被迅速回收或破坏。相反，它们在组织和器官的细胞间隙中积累并持续存在。原纤维本身并没有直接的危害，但淀粉样蛋白的沉积通过扩大细胞之间的距离，特别是细胞与其必需的滋养血液供应的距离，破坏组织结构和功能，导致疾病。这就像一个正在上演的戏剧的完整剧院，逐渐地，然后完全充满了泡沫包装芯片，以至于观众无法看到或听到演员，找到出口，或者最终无法移动甚至呼吸。淀粉样变性是一种难以诊断和治疗的疾病。某些形式的疾病没有治疗方法，而其他形式的治疗方法毒性很大和/或疗效有限。现有的治疗方法旨在减少每种情况下特定淀粉样蛋白形成蛋白的数量，或者干扰其向淀粉样蛋白原纤维的转化。这些方法有时会产生临床效益，但即便如此，许多患者治疗得太晚，在受益之前就死亡了。因此，淀粉样变性的世界领导者马克·佩皮斯教授设计了一种新颖的方法。他使用特殊设计的抗体来激活人体的自然防御机制，直接从组织中去除淀粉样蛋白。这种方法被证明是成功的，首先在实验动物身上，然后在淀粉样变性患者身上，提供了概念的临床证明。与2018年诺贝尔奖获得者、抗体药物领域的世界领先权威格雷格·温特爵士（Sir Greg Winter FRS）一起，Immutrin有限公司成立，旨在创造和开发针对淀粉样变性的新型、变革性抗体治疗方法。令人兴奋的进展带来了一系列独特的新抗体，现在已经准备好进入下一个药物开发阶段，这些抗体将转化为安全有效的人体形式，可以在患者身上进行临床试验。

Amyloidosis is a group of rare but very serious, usually fatal diseases caused by the body's own proteins. Normally, proteins are safely destroyed or recycled at various times after production and are replaced by newly produced molecules to conduct their functions. However, there are about 30 different human proteins that tend to behave differently. Instead of being simply and safely destroyed and replaced, these proteins instead clump together in long strings to form microscopic, thread-like fibres, called amyloid fibrils. Mysteriously, for reasons that are not understood, amyloid fibrils are not promptly recycled or destroyed. Instead, they accumulate and persist in the spaces between cells in tissue and organs. The fibrils themselves are not directly harmful but, by enlarging the distance between cells and, especially, the distance of cells from their essential nourishing blood supply, amyloid deposits damage tissue structure and function, leading to disease. It is as if a full theatre with a play in progress was progressively and then completely filled with foam packing chips so that the audience could not see or hear the actors, find the exits, or, eventually, move or even breathe.Amyloidosis is difficult to diagnose and very challenging to treat. No treatments exist for some forms of the disease whilst treatments for other forms are very toxic and/or have limited efficacy. Existing treatments aim to reduce the amount of the particular amyloid-forming protein in each case, or to interfere with its conversion into amyloid fibrils. These approaches sometimes produce clinical benefit but, even so, many patients are treated too late and die before they can benefit.A novel approach was therefore devised by Professor Sir Mark Pepys FRS, a world leader in amyloidosis. He used specially designed antibodies to activate the body's natural defence mechanisms to directly remove amyloid from the tissues. This approach has proved successful, first in experimental animals and then in amyloidosis patients, providing clinical proof of concept. Together with Sir Greg Winter FRS, Nobel Laureate 2018, and world leading authority on antibody drugs, Immutrin Ltd was founded to create and develop novel, transformative, antibody treatments for amyloidosis.Exciting progress has delivered a unique range of new antibodies, now ready for the next drug development stage, which is conversion into a safe and effective human form that can be clinically tested in patients.