Immunotherapy for amyloidosis

30年来，MRC一直支持我在一种罕见疾病--淀粉样变病--上的工作。我们已经发现了许多关于这种疾病和血液中一种正常蛋白质的已知信息，这种蛋白质被称为血清淀粉样蛋白P成分(SAP)，它导致了这种疾病。我们的MRC资助的SAP研究使我们发明了一种新的诊断测试，该测试在淀粉样变性患者的治疗和存活率方面有了显着的改善。我们还建立了英国国民保健系统国家淀粉样变性中心，这是世界领先的淀粉样变性诊断和治疗中心-S。我们的病人的存活率在其他任何地方都是最好的。然而，导致千分之一人口死亡的淀粉样变性仍然是一种几乎普遍存在的致命疾病。阿尔茨海默病、S病和成熟期糖尿病都与淀粉样蛋白有关，给患者和照顾者带来了长期的痛苦，给社会带来了巨大的代价。我们现在已经发明了专门针对SAP和淀粉样蛋白的新药，并在与人类疾病非常相似的动物模型中产生临床益处。我们最先进的药物可以去除血液中的SAP，有助于减缓淀粉样变性患者的疾病进展，但这是不够的。我们现在已经开发了另一种新的治疗方法，使用SAP的抗体，它完全消除了导致疾病的淀粉样沉积。我们的成就给世界第二大制药公司葛兰素史克留下了深刻的印象，它已经同意与我们合作开发这些药物。他们坚持认为，我们的大学研究团队在漫长、困难和极其昂贵的药物开发过程中分担早期风险。因此，他们故意不为我们的方案部分提供资金。目前的建议是为我们的贡献寻求必要的资金，而GSK则进行他们自己的内部开发工作。这对于MRC和最终将从潜在的挽救生命的新疗法中受益的患者来说，具有非常好的价值。在这里提出的实验室研究的推动下，葛兰素史克的合作将使我们的关键发明尽快进入临床试验，并在拨款的3年内，我们现在寻求MRC支持的基本实验室工作将转化为患者的福利。

For 30 years the MRC has supported my work on a rare disease known as amyloidosis. We have discovered much of what is known about this condition and about a normal protein in the blood, known as serum amyloid P component (SAP), which contributes to the disease. Our MRC funded research on SAP led us to invent a new diagnostic test which has delivered significant improvements in treatment and survival of amyloidosis patients. We went on to establish the UK NHS National Amyloidosis Centre, the world?s leading centre for diagnosis and management of amyloidosis. The survival of our patients is not bettered anywhere else. However amyloidosis, which is responsible for the death of one per thousand of the population, is still an almost universally fatal disease. Alzheimer?s disease and maturity onset diabetes, both of which are associated with amyloid, inflict prolonged suffering on patients and carers, at great cost to society. We have now invented new medicines that specifically target SAP and amyloid, and produce clinical benefit in animal models which closely resemble human disease. Our most advanced drug, that removes SAP from the blood, helpfully slows disease progression in amyloidosis patients but this is not sufficient. We have now developed another novel treatment, using antibodies to SAP, which completely removes the amyloid deposits that cause disease. Our achievements have so impressed GlaxoSmithKline, the second largest pharmaceutical company in the world, that it has agreed to collaborate with us to develop these medications. They have insisted that our university research team shares the early risk in the long, difficult and extremely costly process of drug development. They are therefore deliberately not funding our component of the programme. The present proposal seeks the funding necessary for our contribution, while GSK conduct their own in house development work. This represents extraordinarily good value for the MRC and for the patients who will ultimately benefit from potentially life saving new treatments. Enabled by the laboratory research proposed here, the GSK collaboration will bring our key inventions into clinical trials as soon as possible and, within the 3 year period of the grant, the basic laboratory work, for which we now seek MRC support, will translate towards benefits for sick people.