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: 10530012
• 负责人: Benjamin Natelson
• 金额: $ 10.22万
• 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: 2021-12-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10530012
• 关键词: Aftercare; American; Anxiety; Bathing; Bioinformatics; Biological; Biological Markers; Body Fluids; Brain; Cerebrospinal Fluid; Chronic Fatigue Syndrome; Clinical; Coupled; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Etiology; Fatigue; Feeling; Foundations; Fractionation; Future; Goals; Health; Human Resources; Individual; Label; Laboratories; Lead; Mass Spectrum Analysis; Medical; Methodology; Methods; Molecular; Neurologic; Organ; Outcomes Research; Patients; Pharmaceutical Preparations; Phase; Physicians; Positioning Attribute; Proteins; Proteome; Proteomics; Publishing; Research; Sampling; Scientist; Site; Stigmatization; Strategic Planning; Syndrome; Technology; Testing; Time; United States National Institutes of Health; base; biomarker discovery; biomarker identification; candidate marker; clinical diagnosis; diagnostic biomarker; experience; instrumentation; member; nervous system disorder; novel; operation; potential biomarker; protein biomarkers; specific biomarkers; statistics; 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.

肌痛性脑脊髓炎/慢性疲劳综合症（ME/CFS）是一种病因不明的严重致残性疾病。 它直接影响超过一百万美国人。缺乏有效的生物标志物来区分这一点 其他以疲劳为特征的疾病导致诊断不确定性，结果呈阴性 对患者的后果：医疗从业者通常不相信疾病是真实的，从而导致他们 告诉患者他们没有任何问题 – 使患者产生焦虑感和存在感 被污名化。最近的研究指出大脑可能是导致 ME/CFS 的原因。如果我们可以 识别最相关部位的一种或多种生物标志物，即沐浴大脑的脑脊液，这些发现 将简化诊断并加速研究——结果可能会导致新的治疗策略。 直到过去几年，技术还没有充分发展来实现这一目标。那不再是那个 案件。该提案的具体目标是确定蛋白质生物标志物或生物标志物 ME/CFS 的诊断。为了实现这一目标，我们将利用新的技术进步， 许多是由我们团队成员开发的。我们初步公布的数据表明，存在生物 ME/CFS 的基础以及生物标志物确实存在。但我们不知道哪些在大多数情况下最常见 患者。因此，虽然我们早期的研究结果是一个积极的指标，但现有的技术并不是 足够复杂，可以提供定量数据来定义那些将 ME/CFS 与 健康对照或患有与疲劳相关的其他神经系统疾病的患者。为此，我们将使用 从 35 名未服用脑活性药物的 ME/CFS 患者中采集脑脊液样本， 确定众多候选蛋白质中哪些单独或组合存在于最大数量的蛋白质中 ME/CFS 患者。我们将使用蛋白质分离和质谱的先进组合 为了实现这一目标，目前所有这些方法都在实施。我们处于独特的位置来实现 我们的具体目标，因为我们有： 所需的样本已经储存，一个由医生科学家组成的团队， 质谱和蛋白质组学领域的领先先驱、统计学和生物信息学专家、技术专家 人员到位，并且对所有方法都有经验。