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

描述(申请人提供)：中风是美国第三大致死原因，也是导致长期严重残疾的主要原因。每年约有70万美国人患上新发或复发的中风。仅在2006年，估计就有579亿美元用于支付这些人与中风相关的医疗和残疾护理。中风的诊断可能很困难，因为各种各样的症状通常与其他情况相同。尽管已经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方法来诊断这种情况。CT成像是评估中风患者的一种常用方法，但它不是一种可靠的检测血栓的方法。急性缺血性中风的药物治疗只有在症状出现后三个小时内使用才有效。只有3%-5%的患者在足够的时间内到达医院。因此，需要改进诊断方法。一些研究小组正在进行详细的研究，以评估单个生物标记物在缺血性中风中的表达，以用作诊断工具。然而，测量血浆或血清中细胞因子、趋化因子或其他生物标志物水平的标准方法是使用酶联免疫吸附试验(ELISA)一次一个地进行测量。对每个假定的生物标志物进行一次一次的评估需要大量的时间、成本和样本量。显然，没有任何单一的分子标记或一小群标记能够准确地对高危个体进行分类。因此，系统地识别蛋白质谱、预测临床事件的风险、评估治疗反应和确定潜在机制的能力受到严重限制。基于微球的多重免疫分析技术的最新发展为快速检测大量血浆蛋白抗原提供了一种有效的方法。基于规则的医学已经将这种方法扩展到使用非常小的样本量(10-20？L)来执行血液蛋白质的多分析轮廓(MAP)。这项技术非常适合于并行筛选大量标记物，以识别与缺血性中风相关的蛋白质谱。RBM与Charles River实验室(CRL)合作，建议以易中风的大鼠为模型，确定与缺血性中风相关的生物标记物模式。预计从该计划获得的生理标准可能被用来更好地定义疾病的病理机制，并识别可能适用于人类的缺血性中风的疾病生物标志物。2003年，美国每15人中就有1人死于中风。这些死亡中约有50%发生在医院外。识别缺血性中风症状前阶段的个体以及缺血性中风的高危个体的新的生物标志物模式，将提供更快速的诊断，允许改进对病情的管理，并将为开发和评估新的治疗方法提供框架。在美国，中风是第三大致死原因，也是导致长期严重残疾的首要原因。目前的临床诊断方法是在症状出现时进行诊断，这些症状可能差异很大，如果不及时诊断，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的个体以及中风的高风险个体的新的生物标志物模式，将通过提供更快速的诊断，从而改善对病情的管理，从而对公共卫生有很大的好处，并将为开发和评估新的治疗方法提供一个框架。

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.