Project 2 Summary. Circulating Signals of ME/CFS
Individuals with ME/CFS experience a multitude of disabling symptoms such as fatigue, pain,
unrefreshing sleep, cognitive difficulties, orthostatic intolerance, and post-exertional malaise
(PEM). PEM is the inability to increase physical or mental effort without symptom exacerbation
and it greatly limits the quality of life of ME/CFS patients. In this project, we will learn more
about the tissues and organs affected during and after exercise when ME/CFS patients are
experiencing PEM. We have conducted a study in which ME/CFS and healthy sedentary control
subjects have undergone two successive cardiopulmonary exercise tests (CPETs). As well as
obtaining extensive clinical and exercise physiology data, we have collected blood samples from
these subjects at four time points: before exercise (baseline), immediately after the first CPET,
after a 24 hour recovery period, and immediately after the second CPET. We have already
measured thousands of metabolites and proteins in these samples and measured gene
expression in subpopulations of immune cells. In this project, using the same plasma samples
from the longitudinal exercise study, we will examine novel types of signals that circulate in
blood: Cell-free ribonucleic acid (RNA) and extracellular vesicles (EVs). Cell-free RNA is
released into the blood from dying cells in circulation or from various tissues throughout the
body. EVs are membrane-enclosed bodies that travel through the blood from different tissues
and can deliver protein, RNA, and other signaling molecules. EVs provide information about
tissues such as the brain that could otherwise not be obtained without invasive biopsy. We will
determine which tissues released the cell-free RNA and the EVs into circulation. Learning about
how the content and origin of these signals changes in ME/CFS patients compared to controls
before and after exercise may reveal disruptions in pathways that lead to PEM and provide
clues about additional tissues involved in PEM. We will also quantify the protein and RNA cargo
inside EVs, which can inform us about the modulatory effect the EVs may have in recipient
cells. Recent work also implicates disruption of the tissue that lines the inside of blood vessels
(endothelium). We will culture endothelial cells with plasma and EVs from ME/CFS patients and
controls at baseline to learn if molecules causing endothelial dysfunction in ME/CFS originate
inside or outside EVs. The wealth of data we will have from the same subjects will be used to
look for biomarkers to develop a diagnostic test for ME/CFS. We will also integrate these
different types of data to see if we can define clinically relevant subsets of ME/CFS patients.
National Institute of Allergy and Infectious Diseases
CFDA Code
DUNS Number
872612445
UEI
G56PUALJ3KT5
CCV3WG2JG248
D4H1NV4APKP3
ELS2M3C6V2S5
EQA8NBEN9WD5
FFAZGE9NH3M8
K6JRCJJXFET1
M8FBSLHASMT3
P4LRVQT1H4K5
PJUVN8AT5416
RT1JPM9UMGM5
ZBMGUAZYFGC4
ZMP8BDLJTUW9
Project Start Date
30-September-2017
Project End Date
31-March-2028
Budget Start Date
01-April-2024
Budget End Date
31-March-2025
Project Funding Information for 2024
Total Funding
$774,296
Direct Costs
$489,381
Indirect Costs
$284,915
Year
Funding IC
FY Total Cost by IC
2024
National Institute of Allergy and Infectious Diseases
$774,296
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5U54AI178855-07 8999
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