Proteomic identification of Myalgic encephalomyelitis/chronic fatigue syndrome

肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种病因不明的致残性疾病。 它直接影响了100多万美国人。缺乏有效的生物标记物来区分这一点 以疲劳为特征的其他疾病的情况导致诊断不确定，呈阴性 对患者的后果：通常，健康从业者不相信疾病是真实的--因此导致他们 告诉病人这没什么不对的--让病人产生焦虑和一种 被羞辱了。最近的研究指出，大脑可能是负责ME/CFS的器官。如果我们可以 在最相关的部位确定一个或多个生物标记物，脑脊液沐浴大脑，这些发现 将简化诊断和加速研究--这些结果可能导致新的治疗策略。 直到过去几年，技术还没有发展到足以实现这一目标。这不再是 凯斯。这项提议的具体目标是识别一个或多个蛋白质生物标记 ME/CFS-All-All诊断。为了实现这一目标，我们将利用新的技术进步， 许多都是由我们团队的成员开发的。我们公布的初步数据表明，有一种生物学上的 ME/CFS的基础，以及生物标记物的存在。但我们不知道哪些是最常见的 病人。因此，虽然我们早期研究的结果是一个积极的指标，但可用的技术并非如此 足够复杂，足以提供定量数据来定义那些将ME/CFS与 健康对照或其他与疲劳相关的神经疾病患者。为此，我们将使用 从35名ME/CFS患者采集的脑脊液样本，未服用脑活性药物， 确定许多候选蛋白质中的哪一种单独或组合存在于最多的 我/CFS患者。我们将使用先进的蛋白质分离和质谱学相结合的方法 方法，所有这些方法目前都在运行，以实现这一目标。我们处于一个独特的位置来完成 我们的具体目标是因为我们有：所需的样本已经储存，一个内科科学家团队， 质谱学和蛋白质组学的领先先驱，统计学和生物信息学的专家，技术 人员到位，对所有方法都有经验。

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.