THE EFFECT OF DIFLUNISAL ON HEREDITARY AMYLOIDOSIS

二氟尼柳对遗传性淀粉样变性的影响

• 批准号: 7606257
• 负责人: JOHN L BERK
• 金额: $ 0.66万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-03 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606257
• 关键词: Amino Acid Substitution; Amyloid; Anti-Inflammatory Agents; Computer Retrieval of Information on Scientific Projects Database; Data; Deposition; Diagnosis; Diflunisal; Disease; Familial Amyloid Neuropathies; Funding; Grant; Heart; Hereditary Amyloidosis; Individual; Inherited; Institution; Japan; Life; Liver; Medical; Monitor; Nerve; Numbers; Organ; Patients; Physicians; Placebos; Portugal; Prealbumin; Production; Proteins; Renal function; Research; Research Personnel; Resources; Scientist; Source; Stabilizing Agents; Sweden; Testing; United States; United States National Institutes of Health; pill; prevent; protein folding

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 家族性淀粉样多发性神经病 (FAP) 是一种致命的遗传性疾病，由修饰的肝脏蛋白转甲状腺素蛋白错误折叠引起。一种氨基酸取代会破坏转甲状腺素蛋白的正常聚集，促进单个蛋白质的释放，这些蛋白质异常折叠，形成坚不可摧的蛋白质片，称为淀粉样蛋白。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 年内死亡。不存在任何治疗方法。 我们的数据表明，二氟尼柳是一种市售非甾体抗炎药，可稳定转甲状腺素蛋白簇，防止单个转甲状腺素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，我们建议使用二氟尼柳或空药片（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。这项研究将涉及来自葡萄牙、瑞典、日本和美国的具有 FAP 专业知识的医师科学家，这些地方都有大量 FAP 患者。