Assay and Instrument Development for Diagnosis of Prion Disease

描述（由申请人提供）：朊病毒疾病是由传染性错误折叠朊病毒蛋白（PrPSc）在动物和人类中引起的致命性神经退行性疾病家族。朊病毒疾病可自发发生，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设备污染。朊病毒疾病在出现症状前有长达数年甚至数十年的潜伏期。PrPSc对传统的医疗去污程序具有极强的抵抗力。这些因素引起人们对这些疾病的潜在传播以及对及时诊断工具的需要的重大关切。目前，这种疾病的诊断并不完全基于神经系统疾病的临床症状，只有在死后才能通过脑组织的神经病理和免疫组织化学分析来确诊。迫切需要一种敏感的血液筛查试验，以防止疾病传播的风险。这项小型企业创新研究建议应用一种新的检测方法，结合灵敏的生物传感器技术，开发一种朊病毒疾病的活体检测方法。该试验将能够量化正常和变异的朊病毒。第一阶段的初始目标是血液中5 pg/ml的敏感性，第二阶段将进一步提高。朊病毒疾病具有传染性，

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.