Proteomic identification of Myalgic encephalomyelitis/chronic fatigue syndrome

肌痛性脑脊髓炎/慢性疲劳综合征的蛋白质组学鉴定

• 批准号: 10373504
• 负责人: Benjamin Natelson
• 金额: $ 37.49万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373504
• 关键词: Aftercare; American; Anxiety; Bathing; Bioinformatics; Biological; Biological Markers; Blood; Body Fluids; Brain; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Chronic Fatigue Syndrome; Clinical; Communities; Coupled; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Etiology; Fatigue; Feeling; Fractionation; Future; Goals; Health; Heterogeneity; Human Resources; Individual; Knowledge; Label; Laboratories; Lead; Mass Spectrum Analysis; Medical; Methodology; Methods; Neurologic; Organ; Outcomes Research; Patients; Pharmaceutical Preparations; Phase; Physicians; Positioning Attribute; Proteins; Proteomics; Publishing; Recommendation; Reporting; Research; Research Design; Sample Size; Sampling; Scientist; Site; Source; Stigmatization; Strategic Planning; Technology; Testing; Translating; United States National Institutes of Health; Urine; Work; base; biomarker development; biomarker discovery; biomarker identification; clinical Diagnosis; diagnostic biomarker; disorder control; experience; instrumentation; member; nervous system disorder; novel; operation; potential biomarker; protein biomarkers; statistics; tool; treatment strategy

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a major disabling illness of unknown etiology. It directly impacts more than one million Americans. The lack of validated biomarkers to distinguish this condition from other illnesses characterized by fatigue leads to diagnostic unsurety with negative consequences for the patient: often, health practitioners do not believe the illness is real – thus leading them to tell patients there is nothing wrong with them – producing anxiety in the patient and a feeling of being stigmatized. Recent research points to the brain as the probable organ responsible for ME/CFS. If we could identify one or more biomarkers in the most relevant site, the cerebrospinal fluid bathing the brain, those findings would simplify diagnosis and accelerate research -- outcomes that could lead to novel treatment strategies. Until the past few years, technology was not sufficiently developed to achieve this goal. That is no longer the case. The Specific Aim of this proposal is to identify the protein biomarker or biomarkers that are diagnostic of ME/CFS-at-large. To achieve this Aim, we will take advantage of new technological advances, many developed by members of our team. Our preliminary published data have shown that there is a biological basis for ME/CFS and that biomarkers do exist. But we do not know which are most common across most patients. Thus, while the results of our earlier study were a positive indicator, the technology available was not sophisticated enough to provide quantitative data to define those proteins that will differentiate ME/CFS from healthy controls or from patients with other neurological diseases associated with fatigue. To do this, we will use cerebrospinal fluid samples collected from 35 patients with ME/CFS, taking no brain-active medications, to identify which of the many candidate proteins singularly or in combination are present in the greatest number of ME/CFS patients. We will use an advanced combination of protein fractionation and mass spectrometry methods, all of which are currently in operation, to achieve this goal. We are in a unique position to accomplish our Specific Aim because we have: the required samples already banked, a team of physician-scientists, leading pioneers in mass spectrometry and proteomics, experts in statistics and bioinformatics, technical personnel in place, and experience with all the methods.

肌脑脊髓炎/慢性疲劳综合征（ME/CFS）是未知病因的主要残疾疾病。 它直接影响超过一百万的美国人。缺乏验证的生物标志物来区分这一点 以疲劳为特征的其他疾病的状况导致诊断不良，阴性 对患者的后果：通常，卫生从业者不认为这种疾病是真实的，因此导致他们 告诉病人没有错 - 在患者中产生动画和一种感觉 受污名化。最近的研究表明，大脑是有问题的组织，负责ME/CFS。如果可以的话 在最相关的部位识别一种或多种生物标志物，脑脊液沐浴大脑，这些发现 将简化诊断和加速研究 - 可能导致新型治疗策略的结果。 直到过去几年，技术才得以实现这一目标。那不再是 案件。该建议的具体目的是确定蛋白质生物标志物或生物标志物 ME/CFS-AT诊断。为了实现这一目标，我们将利用新的技术进步， 许多由我们团队成员开发的。我们的初步发布的数据表明，有一个生物学 我/CFS的基础和生物标志物确实存在。但是我们不知道大多数最常见的是 患者。尽管我们较早的研究的结果是一个积极的指标，但可用的技术不是 足够软以提供定量数据来定义那些将使我/CF与 健康对照或与疲劳有关的其他神经系统疾病的患者。为此，我们将使用 从35例ME/CF患者收集的脑脊液样品，不服用脑活动药物， 以最大数量的数量显示了众多或组合的许多候选蛋白中的哪种 我/CFS患者。我们将使用蛋白质分馏和质谱法的高级组合 目前正在运行的方法，以实现此目标。我们处于独特的位置 我们的具体目标是因为我们有：已经需要的样本，一个身体科学家团队， 质谱和蛋白质组学，统计和生物信息学专家的领先开拓者，技术 人员到位，并经验所有方法。