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: 8143496
• 负责人: Nancy Grace Klimas
• 金额: $ 52.55万
• 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/8143496
• 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; Endocrine system; Entropy; Equation; Equilibrium; Exercise; Failure; Female; Fibromyalgia; Flow Cytometry; Foundations; Gender; Gene Expression; Genes; Graph; Health; 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; information model; network models; novel; predictive modeling; 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症（CFS）作为一个日益增长的公共卫生问题的严重程度和范围，以及当前急性疾病研究模型不足以解决影响体内多个调节系统的复杂疾病。这种疾病跨越种族、性别和社会经济地位，影响社会各阶层，每年给美国经济造成的生产力损失估计达 90 亿美元，医疗保健支出高达 240 亿美元。此外，并发症和共病可能很严重，包括心血管疾病和癌症，这进一步增加了风险。研究表明，免疫、内分泌和神经系统都会受到影响。尽管这些系统在密切协作中发挥作用，但仍继续使用传统的逐项方法对慢性疲劳综合症进行研究，重点关注个体神经内分泌和免疫成分的失效。假设：我们假设 CFS 不仅是由于组件故障造成的，更重要的是，可能是由于连接这些组件的调节功能显着恶化所致。我们将通过运动挑战刺激压力反应及其对神经、内分泌和免疫系统的调节来测试调节适应性。目的：本研究的目的是通过三种方式提高我们对 CFS 发病机制的理解：（i）通过使用大规模分子分析对身体多个调节系统的状态进行全面评估，ii）通过使用信息论将这些不同的数据整合到描述这些生理系统之间相互作用的单一可解释图谱中，以及 iii）通过使用网络理论的新颖元素来研究这些信号网络的结构并隔离信号网络的变化 可能特定于 CFS 的“接线”。在这些地图中，我们还将捕获总体稳态控制对运动压力的动态响应。这种对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被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用于执行候选临床试验的计算机辅助设计，其方式与模拟用于培训机组人员的方式大致相同。通过将 CFS 模拟为改变但稳定的控制程序，可以设计治疗方案，利用新的稳态规则将整个系统重定向到正常静息状态和对活动的正常反应模式。