Assay and Instrument Development for Diagnosis of Prion Disease

描述(申请人提供)：Prion病是一种致命的神经退行性疾病，由动物和人类的传染性错误折叠Prion蛋白(PrPSc)引起。Prion疾病可自发发生，并可通过多种途径感染：食用受污染的食物、输血、器官和组织移植以及医疗器械的污染。Pron疾病在出现症状之前有一段数年甚至数十年的潜伏期。PrPSc对传统的医学净化程序具有极强的抵抗力。这些因素引起了人们对疾病的潜在传播以及及时诊断工具的需要的重大关切。目前根据神经功能障碍的临床体征在生前诊断不完善，只有在死后才能通过脑组织的神经病理学和免疫组织化学分析来证实。迫切需要一种灵敏的血液筛查测试，以防止疾病传播的风险。这项小型企业创新研究计划应用一种新的检测方法，结合灵敏的生物传感器技术，来开发一种针对普恩病毒疾病的活体测试。这项检测将能够量化正常和变异的普恩病毒。在第一阶段中，敏感性的初始目标是血液中的5pg/ml，第二阶段将进一步改善。 致命的，并且没有已知的治疗方法。奶牛中的普恩病毒病，俗称“疯牛病”，可以传染给人类。高度敏感的检测可以防止受感染的动物进入食物链。对感染者的早期诊断基本上可以消除将疾病传播给其他人的机会，还将改善血液和组织供应的安全性。目前的测试都是使用脑组织的尸检。这项提议是开发一种灵敏的血液测试来在疾病的早期阶段发现疾病。

DESCRIPTION (provided by applicant): Prion diseases are a family of fatal neurodegenerative diseases that are caused by infectious misfolded prion proteins (PrPSc) in both animals and humans. Prion diseases can occur spontaneously and can be contracted by multiple routes: consumption of contaminated foods, blood transfusion, organ and tissue transplant, and contamination of medical devices. Prion diseases have a years-, and even decades-long incubation period before onset of symptom. PrPSc are extraordinarily resistant to classic medical decontamination procedures. These factors raise major concerns about potential transmission of the diseases and the need for tools for timely diagnosis. Currently the diseases are diagnosed antemortem imperfectly based on clinical signs of neural disorders, and confirmed only postmortem by neuropathological and immunohistochemical analysis of brain tissue. A sensitive blood screening test is urgently needed for protecting against the risk of disease transmission. This Small Business Innovation Research proposes to apply a novel assay, coupled with sensitive biosensor technology, to develop a living test of prion disease. The assay will be able to quantify normal and variant prions. The initial goal for sensitivity in Phase I is 5 pg/ml in blood with further improvement to be made in Phase II. Prion diseases are infectious, fatal, and have no known cure. Prion disease in cows, commonly known as "mad cow disease", can be transmitted to humans. Highly sensitive tests can prevent infected animals from entering the food chain. Early diagnosis of infected individuals could essentially eliminate the chance of transmitting the disease to others and will also improve the safety of the blood and tissue supplies. Current tests are all postmortem assays using brain tissue. This proposal is to develop a sensitive blood test to detect the disease in its early stage.