Assay and Instrument Development for Diagnosis of Prion Disease

描述（由申请人提供）：朊病毒病是一种致命的神经退行性疾病家族，由动物和人类的传染性错误折叠朊病毒蛋白（PrPSc）引起。朊病毒疾病可以自发发生，并可以通过多种途径感染：食用受污染的食物、输血、器官和组织移植以及医疗器械污染。朊病毒疾病在症状出现之前有数年甚至数十年的潜伏期。PrPSc对传统的医疗净化程序具有非凡的抵抗力。这些因素引起了人们对这些疾病的潜在传播和及时诊断工具的需要的重大关切。目前，这些疾病在死前诊断不完全基于神经系统疾病的临床体征，并且仅在死后通过脑组织的神经病理学和免疫组织化学分析来证实。迫切需要一种敏感的血液筛查试验来预防疾病传播的风险。这项小型企业创新研究提出了一种新的检测方法，结合敏感的生物传感器技术，开发朊病毒疾病的活体检测。该测定将能够定量正常和变异朊病毒。第一阶段的初始目标是血液中的灵敏度为5 pg/ml，第二阶段将进一步改善。朊病毒疾病具有传染性， 致命的，没有已知的治疗方法。牛的朊病毒病，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。对受感染者的早期诊断可以基本上消除将疾病传播给他人的机会，还将提高血液和组织供应的安全性。目前的测试都是使用脑组织的死后分析。这项建议是开发一种敏感的血液测试，以在早期发现这种疾病。

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.