I am going to quote a big block of this letter:
"The team came together in 2011 at the request of NIH director, Francis Collins, to rigorously review evidence linking XMRV to ME/CFS. After XMRV was found to be a laboratory contaminant we continued under the auspices of the Hutchins Family Foundation- Chronic Fatigue Initiative and a patient-led crowdfunding initiate, The Microbe Discovery Project, to build an integrated, multicenter program focused on pathogen discovery, microbiome research, proteomics, metabolomics and epigenetics. With the assistance from the ME/CFS community we have amassed detailed questionnaire data for epidemiology and hundreds of blood, stool and saliva samples for microbiome, proteomic and metabolomic analyses. Our team has already identified differences between short- and long-term illness duration subsets of patients based on CSF cytokine data and has early findings that we believe will impact the lives of thousands of patients.
In 2015, we began a one-year NIH-funded study to recruit and enroll an additional 125 ME/CFS cases and 125 healthy controls across five geographically distinct clinical sites. Each of these subjects are rigorously screened by clinical experts in ME/CFS. A wide range of biological samples are to be collected at four time points to account for seasonal variation. We have already collected 25% of the projected questionnaire data and samples; thus, we are on track to have the world’s most comprehensive ME/CFS database and sample repository by early 2017. We meet in monthly teleconferences to review progress in meeting study objectives and to focus our limited analytical resources on the most urgent research questions. Drs. Major and Unger provide linkage to the National Institutes of Health and the Centers for Disease Control, respectively, thereby insuring integration of extramural and intramural efforts.
The following list briefly describes gaps in knowledge that we have discussed as highest priority. I have also shared this list independently with the Director of the NINDS, Walter Koroshetz.
Microbiome (bacteriome, mycobiome, virome)
• Characterize the microbiome of the blood, oropharynx and gastrointestinal tract in an effort to identify potential triggers of immune response or metabolic dysfunction.
Proteomics
• Identify biomarkers in blood and cerebrospinal fluid that can be used for diagnosis, prognosis, and to follow the course of disease and response to interventions. Biomarkers may also provide insights into potential therapeutic targets.
Metabolomics
• Identify potential diagnostic and therapeutic targets.
Immunology
• Identify biomarkers for diagnosis, prognosis as well as potential therapeutic targets; determine history of exposure to infectious agents that may trigger onset or exacerbation of ME/CFS.
Genetics/Epigenetics
• Identify gene variants that may be associated with specific clinical presentations or phenotypes that may predict course of illness or response to varying therapeutic interventions.
• Identify epigenetic signatures that may be associated with ME/CFS and that may correlate with infectious or other triggers.
Brain Imaging
• MRI and fMRI studies to enhance understanding of the neural circuitry and inflammation associated with ME/CFS.
To meet these urgent research needs, the CfS for ME/CFS will prioritize the following components in our “center without walls”:
1) Patient Registry
2) Biobank
3) Clinician Training Program
4) Clinical Trials
Patient Registry
The Patient Registry willprovide ready access to the pre-qualified, well-characterized and consented cases and controls required to obtain samples, test hypotheses, validate assays, assess the safety and efficacy of therapeutic interventions and pursue exploratory research. Questionnaires provide a wealth of qualitative and quantitative data. This registry would include instruments to assess quality of life, cognitive dysfunction, medical history, medications, and other metrics. Standardization will be key to comparing results across various studies. To maximize the registry’s utility, common data elements must be identified and incorporated and diagnostic criteria must be standardized across studies. Existing study subjects tend to be demographically homogenous, which may skew scientific findings. To diversify the sample set, studies must actively recruit underrepresented groups, such as males and ethnic minorities.
Biobank
A biological sample repository should be readily available to researchers across all disciplines and geographic locations. Samples will represent a wide range of human tissues and be acquired and processed at all sites in strict adherence to established protocols. Aliquots will be created in predesignated sizes for each sample type in anticipation of sample size requirements for downstream analyses to minimize excess thaw/refreeze cycles, ensure that banked samples are of optimal yield and integrity and to preserve the utility of the Biobank for long-term studies, including prospective investigations. Diverse tissue samples, including biopsy material acquired during routine or clinicallyindicated endoscopy/colonoscopy, examinations of suspicious thyroid growths as well as bone marrow biopsies will be included. Eventual integration of the biobank and patient registry would provide an unparalleled comprehensive resource for epidemiologic and physiologic investigations.
Clinician Training Program
Given the reticence of the medical community to accept ME/CFS as a biological illness, it is no surprise that medical schools do not include ME/CFS in their curricula and that there is no existing specialization program. Accordingly, the CfS for ME/CFS is designing a two-year Masters-level training program that will include rotations in neurology, immunology, rheumatology, clinical epidemiology, statistics and health services training to provide the interdisciplinary clinical and research knowledge needed to quickly diagnose and administer treatment to ME/CFS patients and to expand the pool of potential recruits for research studies.
Clinical Trials
As this group and others discover more clues to the biological underpinnings of this disease, a clinical trials program will enable research to be rapidly translated into clinical practice. A Clinical Trials Unit should be positioned to rigorously examine interventions, including probiotic/nutritional, biological (e.g., immune regulators; anti-cytokine antibodies), medication and potentially, microbiome-related (e.g., fecal microbiome transplantation, other) approaches. Subject recruitment would be enabled by the Patient Registry. "