Study of Chronic Fatigue Syndrome using comprehensive molecular profiling with ne

使用新的综合分子谱分析慢性疲劳综合症的研究

• 批准号: 8051249
• 负责人: Nancy Grace Klimas
• 金额: $ 53.22万
• 依托单位: SOUTH FLORIDA VA FDN/RESEARCH/ EDUCATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051249
• 关键词: Acute; Affect; Biological; Biological Assay; Blood; Blood specimen; Cardiovascular system; Cells; Chronic Disease; Chronic Fatigue Syndrome; Clinic; Clinical; Clinical Trials; Collaborations; Comorbidity; Complex; Computer Simulation; Computer-Aided Design; Cytokine Gene; Data; Databases; Deterioration; Disease; Elements; Endocrine; Entropy; Equation; Equilibrium; Exercise; Failure; Female; Fibromyalgia; Flow Cytometry; Foundations; Gender; Gene Expression; Genes; Graph; Health Expenditures; Hormones; Hour; Immune; Immune system; Individual; Information Systems; Information Theory; Intervention; Knowledge; Leukocytes; Link; Malignant Neoplasms; Maps; Measurement; Measures; Modeling; Molecular Profiling; Nature; Nervous system structure; Neuropeptides; Neurosecretory Systems; Onset of illness; Pathogenesis; Patients; Pattern; Physiological; Plasma; Population; Productivity; Public Health; Race; Research; Rest; Sampling; Schedule; Signal Transduction; Simulate; Societies; Socioeconomic Status; Source; Stress; Structure; Subgroup; Surface; System; Testing; Time; Training; base; biological adaptation to stress; case control; cell type; cohort; cost; cytokine; cytotoxic; design; dosage; fitness; immune activation; improved; network models; novel; predictive modeling; public health relevance; response; simulation; theories; treatment program; virtual

DESCRIPTION (provided by applicant): Significance of this project resides in the magnitude and scope of Chronic Fatigue Syndrome (CFS) as a growing public health concern and in the inadequacy of current acute illness research models for resolving complex disorders affecting multiple regulatory systems in the body. This illness cuts across race, gender and socioeconomic status to affect a wide segment of society with costs to the US economy estimated at $9 billion in lost productivity and up to $24 billion dollars in health care expenditures annually. Moreover complications and co-morbidity can be severe, including cardiovascular illness and cancer, raising the stakes even further. Research has shown that immune, endocrine and nervous systems are all affected. Though these systems function in close collaboration CFS continues to be studied using a traditional piece-by-piece approach focusing on the failure of individual neuroendocrine and immune components. Hypothesis: We hypothesize that CFS results not only from component failure but perhaps more importantly from a significant deterioration of regulatory function linking these components. We will test regulatory fitness by using an exercise challenge to stimulate stress response and its modulation of the nervous, endocrine and immune systems. Objectives: The objective of this study is to improve our understanding of CFS pathogenesis in three ways: (i) by using broad-scale molecular profiling to create a comprehensive assessment of status in several of the body's regulatory systems, ii) by using information theory to integrate this disparate data into a single interpretable map describing the interactions between these physiologic systems and iii) by using novel elements of network theory to study the structure of these signaling networks and isolate alterations in the "wiring" that might be specific to CFS. Embedded in these maps we will also have captured the dynamic response of the overarching homeostatic control to exercise stress. This quantitative knowledge of the rates and directions with which biological information is disseminated through the neuroendocrine immune networks will be used as a basis for simulating response to treatment. Indeed computer simulations of neuroendocrineimmune response will be used to perform computer-aided design of candidate clinical trials in much the same way simulations have been used to train flight crews. By simulating CFS as an altered but stable control program treatment courses can be designed that exploit the new homeostatic rules to redirect the system as a whole to normal resting state and a normal pattern of response to activity.

描述（由申请人提供）：该项目的意义在于慢性疲劳综合征（CFS）作为一个日益增长的公共卫生问题的程度和范围，以及当前急性疾病研究模型在解决影响体内多个调节系统的复杂疾病方面的不足。这种疾病跨越种族，性别和社会经济地位，影响到广泛的社会阶层，估计美国经济每年损失90亿美元的生产力和高达240亿美元的医疗保健支出。此外，并发症和合并症可能很严重，包括心血管疾病和癌症，进一步增加了风险。研究表明，免疫、内分泌和神经系统都会受到影响。虽然这些系统的功能密切合作，CFS继续研究使用传统的一件一件的方法，侧重于个别神经内分泌和免疫组件的故障。假设：我们推测，CFS的结果不仅从组件故障，但也许更重要的是从一个显着恶化的监管功能连接这些组件。我们将通过运动挑战来刺激应激反应及其对神经、内分泌和免疫系统的调节来测试调节适应性。目的：本研究的目的是从三个方面提高我们对CFS发病机制的理解：（i）通过使用大规模的分子特征分析，对该机构的几个监管系统的状况进行全面评估，ii）通过使用信息理论将这些不同的数据整合到描述这些生理系统之间的相互作用的单个可解释的图中，以及iii）通过使用网络理论的新元素来研究这些信号网络的结构，并隔离可能特定于CFS的“布线”中的变化。在这些地图中，我们还将捕捉到总体稳态控制对运动应激的动态反应。生物信息通过神经内分泌免疫网络传播的速率和方向的定量知识将用作模拟治疗反应的基础。事实上，神经内分泌免疫反应的计算机模拟将被用于进行候选临床试验的计算机辅助设计，就像模拟用于培训飞行人员一样。通过将CFS模拟为改变的但稳定的控制程序，可以设计利用新的稳态规则将系统作为一个整体重定向到正常的静息状态和对活动的正常响应模式的治疗过程。