THE EFFECT OF DIFLUNISAL ON HEREDITARY AMYLOIDOSIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 家族性淀粉样多发性神经病（FAP）是一种致命的遗传性疾病，由一种修饰的肝蛋白-转黄蛋白的错误折叠引起。一个氨基酸取代破坏了甲状腺素运载蛋白的正常聚集，促进了单个蛋白质的释放，这些蛋白质异常折叠，形成称为淀粉样蛋白的不可破坏的蛋白质片。最终，淀粉样蛋白沉积在重要器官中，损害功能。通常，FAP患者在诊断后7-15年死亡。不存在任何治疗。 我们的数据表明，二氟尼柳，一种市售的非甾体抗炎药，稳定甲状腺素运载蛋白簇，防止单个甲状腺素运载蛋白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药丸（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。这项研究将涉及在葡萄牙，瑞典，日本和美国的FAP专业知识的医生-科学家-所有这些地方都有大量的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.