ELECTRONIC SENSING OF NEURODEGENERATIVE DISEASE FIBRILS

神经退行性疾病原纤维的电子传感

• 批准号: 6072190
• 负责人: CYNTHIA C. BAMDAD
• 金额: $ 10万
• 依托单位: MINERVA BIOTECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6072190
• 关键词: Alzheimer's disease; amyloid proteins; intermolecular interaction; microelectrodes; monitoring device; nervous system disorder diagnosis; neural degeneration; neurofilament; protein protein interaction; protein structure; technology /technique development

We will develop an electronic technology to detect fibrillar aggregates, which are characteristic of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Our preliminary results (detection of 100 protein molecules) indicate that the enhanced sensitivity of our technology could enable the detection of the earliest biochemical evidence of a neurodegenerative disease, like Alzheimer's disease. This would allow the non-invasive screening of patients by analyzing bodily fluids for characteristic fibrils and provide a quantitative method for assessing the efficacy of drugs in clinical trials. The technology can readily be extended to a MEMS (microelectronic and mechanical system) based array assay to multiplex the screening of drugs to inhibit fibril formation. The technology will also enable the rapid screening of nested sets of peptides to identify sequences that participate in fibril formation. We have chosen Alzheimer's disease as our model system to develop and test the technology because it is an important biological problem, fibril formation of beta-amyloid variants has been well characterized in vitro and a likely target for therapeutic intervention, the protofibril, has been identified. However, the technology can be used as a general tool for detecting any protein-protein, antibody-protein or drug-protein interaction in a high-throughput system. PROPOSED COMMERCIAL APPLICATIONS: The rapid electronic detection of fibrillar aggregates characteristic of neurodegenerative diseases will allow for the commercial development of tests to screen pre-symptomatic patients for disease, to objectively monitor response to therapy in symptomatic patients and to screen for drugs that block fibril formation or their incorporation into aggregates.

我们将开发一种电子技术来检测原纤维聚集体，这是神经退行性疾病的特征，例如阿尔茨海默氏症和帕金森氏病。我们的初步结果（检测100个蛋白质分子）表明，我们技术的敏感性增强可以使检测神经退行性疾病的最早的生化证据，例如阿尔茨海默氏病。这将通过分析体液的特征性原纤维来对患者进行非侵入性筛查，并提供一种定量方法来评估药物在临床试验中的疗效。该技术可以轻松地扩展到基于MEMS（微电源和机械系统）的阵列测定法，以将药物筛选以抑制原纤维形成。该技术还将能够快速筛选嵌套的肽集，以识别参与原纤维形成的序列。我们选择了阿尔茨海默氏病作为我们的模型系统来开发和测试该技术，因为它是一个重要的生物学问题，β-淀粉样变体的原纤维形成在体外表征很好，并且可能是治疗干预的靶标，即原纤维。但是，该技术可用作在高通量系统中检测任何蛋白质蛋白质，抗体蛋白或药物蛋白质相互作用的通用工具。拟议的商业应用：神经退行性疾病的纤维骨聚集体的快速电子检测将允许进行商业开发测试以筛查症状前患者的疾病，以客观地监测有症状的患者对治疗的反应，并筛查纤维化形成或将其掺入聚集的药物。