Biomarker Profiles for Predicting Stroke Using Stroke-Prone Rats as a Model

使用易中风大鼠作为模型预测中风的生物标志物概况

• 批准号: 7273124
• 负责人: James P Mapes
• 金额: $ 9.96万
• 依托单位: RULES-BASED MEDICINE, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7273124
• 关键词: Accounting; Acute; Aging; American; Animal Model; Animals; Antigens; Biological Markers; Blood Proteins; Caring; Cause of Death; Cessation of life; Clinical; Coagulation Process; Collaborations; Condition; Control Groups; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diet; Disease; Enzyme-Linked Immunosorbent Assay; Event; Fatty acid glycerol esters; Health Benefit; Hospitals; Hour; Human; Image; Immunoassay; Inbred SHR Rats; Individual; Ischemic Stroke; Laboratories; Measures; Medical; Medicine; Methods; Modeling; Numbers; Outcome; Patients; Pattern; Personal Satisfaction; Pharmacotherapy; Physiological; Plasma; Plasma Proteins; Proteins; Proteomics; Public Health; Rate; Rattus; Recurrence; Research; Risk; Rivers; Sampling; Screening procedure; Serum; Staging; Standards of Weights and Measures; Stroke; Symptoms; Technology; Therapeutic; Time; United States; X-Ray Computed Tomography; age effect; base; chemokine; cost; cytokine; disability; improved; novel; programs; rapid diagnosis; response; time use; tool

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death and is a leading cause of serious, long-term disability in the United States. A new or recurrent stroke is suffered by ~ 700,000 Americans each year. An estimated 57.9 billion dollars will be spent to cover the stroke-related medical treatment and disability care for these individuals in 2006 alone. Stroke diagnosis can be difficult due to a wide variety of symptoms that are often shared by other conditions. Although extensive research has been conducted on ischemic stroke, there remains no laboratory- based method of diagnosing the condition. Computed tomography (CT) imaging is one common method used to evaluate stoke patients, however, it is not a reliable method for detecting clots. Drug therapy for acute ischemic stroke is only effective if administered within three hours of the onset of symptoms. Only 3-5% of patients reach the hospital in enough time. Thus, improved diagnostic methods are needed. A number of research groups are performing detailed studies to evaluate the expression of individual biomarkers in ischemic stroke for use as a diagnostic tool. However, the standard method for measuring plasma or serum levels of cytokines, chemokines or other biomarkers is to measure them one at a time using Enzyme-Linked Immunosorbent Assay (ELISA). One-at-a-time assessment of each putative biomarker incurs considerable time, cost and sample volume. Clearly, no single molecular marker, or small group of markers, will be able to accurately classify individuals at highest risk. The ability to systematically identify protein profiles, predict risk of clinical events, evaluate therapeutic response, and define underlying mechanisms is thereby limited severely. The recent development of bead-based multiplex immunoassays provides an efficient approach for performing a rapid assessment of large numbers of plasma protein antigens. Rules-Based Medicine (RBM) has extended this approach to perform Multi-Analyte Profiles (MAP) of blood proteins using very small sample volumes (10- 20 ¿L). This technology is well suited for screening large numbers of markers in parallel to identify protein profiles associated with ischemic stroke. RBM, in collaboration with Charles River Laboratories (CRL), proposes to identify biomarker patterns associated with ischemic stroke using stroke-prone rats as a model. It is expected that the physiological criteria obtained from the program may be used to better define the pathological mechanisms of the disease, and to identify disease biomarkers of ischemic stroke that may be applied to humans. Stroke accounted for 1 of every 15 deaths in the United States in 2003. About 50% of these deaths occurred out of hospital. The identification of novel biomarker patterns of individuals in the presymptomatic stages of ischemic stroke, as well as individuals at high risk for having an ischemic stroke, will provide a more rapid diagnosis, allow for improved management of the condition, and will provide a framework for developing and evaluating new treatments. Stroke is the third leading cause of death and is a leading cause of serious, long-term disability in the United States. The current clinical approach to diagnosis is at the onset of symptoms, which can vary greatly, and the outcome can be dire if not diagnosed in time, or if treated improperly. The identification of novel biomarker patterns of individuals in the presymptomatic stages of stroke, as well as individuals at high risk for having a stroke, would be of great public health benefit by providing a more rapid diagnosis, allowing for improved management of the condition, and will provide a framework for developing and evaluating new treatments.

描述（由申请人提供）：中风是美国第三大死亡原因，也是严重长期残疾的主要原因。每年约有70万美国人患新发或复发性中风。据估计，仅在2006年，就将花费579亿美元用于支付这些人与中风有关的医疗和残疾护理。中风的诊断可能是困难的，因为各种各样的症状，往往是由其他条件共享。虽然对缺血性中风进行了广泛的研究，但仍然没有基于实验室的诊断方法。计算机断层扫描（CT）成像是一种用于评估斯托克患者的常用方法，然而，它不是检测血栓的可靠方法。急性缺血性中风的药物治疗只有在症状出现后三小时内给药才有效。只有3%-5%的病人能及时到达医院。因此，需要改进的诊断方法。许多研究小组正在进行详细的研究，以评估缺血性卒中中个体生物标志物的表达，作为诊断工具。然而，用于测量细胞因子、趋化因子或其他生物标志物的血浆或血清水平的标准方法是使用酶联免疫吸附测定（ELISA）一次测量一种。对每种假定的生物标志物进行一次一次的评估会花费大量的时间、成本和样本量。显然，没有一个单一的分子标记，或一小群标记，将能够准确地分类个人在最高风险。因此，系统鉴定蛋白质谱、预测临床事件风险、评价治疗反应和确定潜在机制的能力受到严重限制。基于微珠的多重免疫测定的最新发展为进行大量血浆蛋白抗原的快速评估提供了有效的方法。基于规则的医学（RBM）已经将这种方法扩展到使用非常小的样品体积（10- 20 μ L）进行血液蛋白的多分析物谱（MAP）。该技术非常适合于平行筛选大量标记物以鉴定与缺血性卒中相关的蛋白质谱。RBM与查尔斯河实验室（CRL）合作，提出以易卒中大鼠为模型，鉴定与缺血性卒中相关的生物标志物模式。预计从该计划中获得的生理标准可用于更好地定义疾病的病理机制，并确定可应用于人类的缺血性卒中的疾病生物标志物。2003年，在美国，每15例死亡中就有1例死于中风。这些死亡中约有50%发生在医院外。在缺血性中风的症状前阶段的个体以及具有缺血性中风高风险的个体中识别新的生物标志物模式将提供更快速的诊断，允许改善对病症的管理，并且将提供用于开发和评估新治疗的框架。中风是第三大死亡原因，也是美国严重、长期残疾的主要原因。目前的临床诊断方法是在症状发作时，这可能有很大的差异，如果没有及时诊断，或者如果治疗不当，结果可能是可怕的。识别中风症状前阶段个体以及中风高风险个体的新生物标志物模式将通过提供更快速的诊断而具有巨大的公共卫生益处，从而改善对病情的管理，并将为开发和评估新治疗提供框架。