Proteomic identification of Myalgic encephalomyelitis/chronic fatigue syndrome

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.