THE EFFECT OF DIFLUNISAL ON HEREDITARY AMYLOIDOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 家族性淀粉样多发性神经病(FAP)是一种致命的遗传性疾病，由一种修饰的肝脏蛋白--转氨酶激动素的错误折叠引起。一种氨基酸替代扰乱了转甲状腺素的正常聚集，促进了个别蛋白质的释放，这些蛋白质折叠起来，形成了称为淀粉样蛋白的坚不可摧的片状蛋白质。最终，淀粉样蛋白沉积在重要器官中，损害功能。通常情况下，FAP患者在确诊后7-15年内死亡。目前还没有任何治疗方法。 我们的数据表明，商业上可获得的非类固醇抗炎药二氟尼柳可以稳定转甲状腺素簇，防止单个转甲状腺素分子的释放和淀粉样蛋白的产生。为了测试二氟尼柳预防疾病恶化的能力，我们建议用二氟尼柳或空丸(安慰剂)治疗FAP患者至少两年。监测他们的神经、心脏和肾脏功能。这项研究将涉及葡萄牙、瑞典、日本和美国的内科医生--在FAP方面有专长的科学家--所有这些地方都有大量FAP患者居住。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Familial amyloid polyneuropathy (FAP) is a deadly inherited disease caused by misfolding of a modified liver protein-transhyretin. One amino acid substitution disrupts the normal clustering of transthyretin, promoting release of individual proteins that fold abnormally forming indestructible sheets of protein called amyloid. Ultimately, amyloid deposits in vital organs, impairing function. Typically, FAP patients die 7-15 years after diagnosis. No medical treatment exists. Our data indicate that diflunisal, a commercially available non-steroidal anti-inflammatory agent, stabilizes transthyretin clusters, preventing release of individual transthyretin molecules and production of amyloid. To test the ability of diflunisal to prevent disease worsening, we propose treating FAP patients with either diflunisal or empty pills (placebo) for at least two years. Monitoring their nerve, heart and kidney functions. The study will involve physician-scientists with expertise in FAP located in Portugal, Sweden, Japan and the United States -- all places where large numbers of patients with FAP live.