Research Projects
ME Association funded research on ME/CFS and Long Covid
Below is a list of research papers funded completely or partially by the ME Association, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS), and Long Covid, listed chronologically.
Current Projects
Ramsay Biomedical Research Projects
Overview
- This study investigates whether poor muscle oxygenation and delayed energy recovery contribute to fatigue and post‑exertional malaise (PEM) in ME/CFS.
- Uses two non‑invasive, state‑of‑the‑art techniques:
- Magnetic Resonance Imaging (MRI) to measure phosphocreatine (PCr) recovery — “direct and non‑invasive insight into oxidative energy production.”
- Near‑Infrared Spectroscopy (NIRS) to assess muscle oxygenation using a small light probe — “rapid assessment of muscle oxygenation… involves a small light probe on the skin.”
- Stage 1 (funded, now recruiting): Baseline comparison of muscle metabolism in 20 people with mild ME/CFS and 10 sedentary healthy controls.
- Participants complete MRI, NIRS, blood and urine sampling, questionnaires, and wear a smartwatch; healthy controls also complete a sub‑maximal bike test.
- Stage 2 (funding required): Repeats all assessments during PEM, induced by a supervised sub‑maximal exercise test.
- Researchers expect to see slower PCr recovery, reduced oxygen utilisation, and exercise‑inflated mitochondrial dysfunction during PEM.
- Blood and urine samples will support future research including proteomics, metabolomics, Raman spectroscopy, and micro‑clot analysis.
- Findings could help explain why even small amounts of activity trigger severe PEM and may support development of scalable diagnostic tools such as NIRS.
- Stage 1 is funded thanks to supporters of the Big Give Christmas Challenge.
Overview
- ME/CFS and Long Covid are debilitating illnesses that currently lack validated diagnostic tests.
- Biomarkers in blood offer a promising route to earlier and more accurate diagnosis.
- Previous challenges have included limited sensitivity (detecting very low-level molecules) and specificity (distinguishing overlapping conditions).
- This pilot study uses an advanced, cost-effective technology — ALAMAR Bioscience’s NULISA platform — to measure more than 300 neurological and inflammatory proteins.
- The approach should detect subtle biological changes that previous methods have missed.
- Samples come from well-characterised cohorts via the UK ME/CFS Biobank and the UCLH STIMULATE ICP Long Covid study.
- The study aims to identify biomarkers specific to ME/CFS, and to Long Covid, or shared between both conditions.
- Data analysis will use statistical and machine-learning methods to identify diagnostic signatures.
Introduction
The ME Association (MEA) has committed £1.175 million to a major new research project – its largest ever investment, and the biggest amount any charity has committed to Long Covid (LC) or ME/CFS research.
Since the Covid-19 pandemic began, huge amounts of research have gone into understanding Covid-19 and Long Covid. The MEA has consistently argued that ME/CFS should have been included in this work, because the two conditions show many similarities. The new Rosetta Stone project will finally allow researchers to study them side by side, on a scale never attempted before.
Overview
The aim of this project is to understand what is happening in the body at the cellular and molecular level in people with LC and ME/CFS. The research team will do this by directly comparing biological samples from people with these conditions to those from healthy individuals. By studying these groups side-by-side, they hope to identify the key biological changes that may explain symptoms, offer a guide to future treatments, and supply serum markers to be used both in referral pathways and in stratification for clinical trials. Improve sample preparation and compare fresh versus cryopreserved cells.
They will study:
- Proteins in the blood, to reveal shared disease patterns or underlying mechanisms in LC and ME/CFS
- Immune function, including autoimmune antibodies, autoimmune T cells, different immune cell types, and their metabolic activity, to show common changes that could help explain symptoms.
- Human herpesviruses, such as EBV, HHV-6B, and HHV-7, which are reactivating in these conditions, and how virus levels and T-cell immune responses relate to illness
- and gut microbiome disturbances.
Origin
- Builds on 2019 work by Prof. Ron Davis detecting electrical abnormalities in ME/CFS blood cells.
Initial Study
- Funded by ME Association and ME Research UK in 2023; showed distinct electrical properties in ME/CFS PBMCs vs. healthy controls.
Key Findings
- Suggests ion channel dysfunction and altered ionic composition in ME/CFS cells
- Electrical signatures may distinguish ME/CFS from other conditions
- Supports potential for a diagnostic biomarker
Phase II Goals
- Test a larger, more diverse cohort
- Improve sample preparation and compare fresh vs. cryopreserved cells
- Compare ME/CFS with Long Covid, MS, and healthy controls
- Investigate ion channel mechanisms and test low-dose naltrexone (LDN) as a potential modulator
Previous Research & Observations:
- LDN (Low Dose Naltrexone) has shown safety and effectiveness in chronic conditions like Fibromyalgia.
- Observational studies suggest LDN may improve energy, pain, and sleep in ME/CFS patients, with only minor adverse effects reported.
About Naltrexone:
- Naltrexone is an opiate antagonist approved for alcohol and opiate use disorders.
- Used off-label at low doses for ME/CFS, Fibromyalgia, and Crohn’s disease.
Mechanism of Action (LDN):
- Temporarily blocks certain opioid receptors, increasing their number and sensitivity.
- Enhances circulation of endogenous opiate-like molecules, which are typically reduced in ME/CFS.
- Potential effects include reduced pain and inflammation, improved immune function, and enhanced well-being.
- May counterbalance the pro-inflammatory state associated with early ME/CFS, supporting recovery.
Overview of UK ME/CFS Biobank (UKMEB):
- Established in 2011 to support biomedical research into ME/CFS, which was initially funded by Action for M.E. (AFME), ME Research UK (MERUK) and The ME Association (MEA).
Purpose and Reach:
- Provides high-quality biological samples to research teams worldwide, including:
- UK, Europe, North America, Latin America & the Middle East.
- Known internationally for efficiency and quality.
- Increasing demand for samples reflects its value in advancing ME/CFS research.
Biobank Contents:
- Includes samples from:
- Mild to severely affected ME/CFS patients (ages 18–60)
- Healthy controls
- Patients with neurologically diagnosed multiple sclerosis (MS)
- Types of blood samples stored:
- Serum
- Plasma
- Peripheral blood mononuclear cells (PBMC)
- Red blood cells/granulocyte pellet
- Whole blood
- RNA
Funding and Operations:
- Basic running costs now covered by the MEA Ramsay Research Fund (RRF).
Overview:
- In 2023, the ME Association partnered with the Manchester Brain Bank to support post-mortem research into ME/CFS.
- Through the Ramsay Research Fund, detailed examinations of brain and nervous system tissue—including the spinal cord and dorsal root ganglion—will be carried out on at least five individuals aged 18–50 with a confirmed diagnosis.
- The age limit helps ensure findings are specific to ME/CFS rather than age-related changes. Those wishing to donate must meet the same diagnostic and age criteria. Research focuses on the biological, mechanisms underlying ME/CFS, with an emphasis on:
Ramsay Healthcare Research Projects
Background
- There is currently a lack of reliable tools in ME/CFS services to assess symptoms and disability.
- Phase I of this research project co-produced validated PROMs with patients and clinicians.
Phase II of this research project will:
- Disseminate findings via peer-reviewed publications.
- Expand the toolkit with three new resources (co-morbidities checklist, care plan, child-friendly version).
- Implement widely via website and digital apps for individuals and NHS services.
Background
- ME/CFS research suffers from inconsistent diagnostic criteria.
- This project aims to develop a standardised, patient-informed framework to improve research quality and comparability.
Key activities
- Surveying patients, clinicians, and researchers
- Conducting a scoping review of symptom severity measures
- Hosting a panel discussion at IACFS/ME 2025 to explore controversies and build consensus
Planned outputs
- A consensus framework
- A published report
- Practical guidance for researchers
Background
- ME/CFS significantly affects health, yet little research has examined its impact on pregnancy outcomes for both birthing parent and child.
- Lack of evidence creates uncertainty around family planning, pregnancy care and postpartum care.
Recent Research
- A mixed-methods systematic review was previously conducted by the research group on ME/CFS and pregnancy, funded by Newcastle Healthcare Charity.
- This review identified key knowledge gaps and the need for high-quality research is needed to inform evidence-based clinical guidelines.
Pilot Study Goals
This research aims to:
- Establishing key research priorities from the perspectives of individuals with ME/CFS and their healthcare providers regarding pregnancy.
- Exploring experiences, attitudes, and perceptions related to pregnancy and ME/CFS.
- Investigating decision-making around pregnancy among patients and professionals, including doctors, midwives, and health visitors.
- Identifying existing clinical data collection practices related to ME/CFS and pregnancy to shape future research.
Student Research – PhD Funded Projects
Background
- ME/CFS is hard to diagnose and treat due to its complex biology and lack of biomarkers.
- Metabolomics, a branch of “omics,” studies small molecules to find disease-specific patterns.
- Mass spectrometry (MS) helps detect these molecules, but identifying unknowns is challenging.
- Traditional tools like Nuclear Magnetic Resonance (NMR) are slow and limited—advanced methods and modelling are needed.
Project Overview
- Goal: Identify unknown molecules in ME/CFS patients and healthy controls to find potential biomarkers.
- Uses of advanced tools across different research sites, including ion mobility mass spectrometry combined with liquid chromatography and tandem MS (LC-MS/MS).
- Combining lab techniques with computer modelling (Universal Fragmentation Model -UFM) to predict molecular behaviour.
- Findings will be validated using NMR or microED, which then can be mapped to confirm molecules to disease pathways.
- Hopefully findings will inform new diagnostics and treatment strategies.
Background
- Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive method used to stimulate the vagus nerve via the ear, showing promise for conditions like epilepsy, depression, and migraines, and potential benefits in memory, inflammation, and pain.
- Interest in taVNS is growing, however, to date only one former study has been conducted (Natelson et al., 2023)
Study Aims
This study will help prepare for more rigorous research into taVNS as a potential treatment for ME/CFS through:
- Assessing the feasibility of a full-scale trial (recruitment, adherence, etc.),
- Determining appropriate sample size and outcome measures,
- Understanding patient experiences with taVNS,
- Evaluating the treatment’s safety.
Completed Projects
Definition and Symptoms:
- Dysautonomia is a clinical syndrome involving dysfunction of the autonomic nervous system (ANS).
- The ANS regulates vital functions like heart rate, digestion, and body temperature.
- Common symptoms include:
- Abnormal heart rate fluctuations
- Headaches
- Anxiety
- Excessive or reduced sweating
- Severe fatigue
Association with ME/CFS and Long Covid:
- Dysautonomia is present in over half of patients with ME/CFS and Long Covid.
- Despite prevalence, standardized treatment options remain limited.
Need for Research:
- The persistent and debilitating nature of symptoms underscores the need for effective, evidence-based management strategies.
Study Objective:
This pilot study aims to:
- Develop and evaluate a personalized Dysautonomia Management Protocol (DMP)
- Improve symptom management
- Enhance quality of life
- Lay the groundwork for future large-scale research initiatives
Research History:
- Since 2016, the ME Association has funded multiple research projects at the University of Oxford.
- Research focuses on the biological, mechanisms underlying ME/CFS, with an emphasis on:
- Mitochondrial Dysfunction
- Oxidative Stress
- Metabolic Abnormalities
The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology
Clarke, KSP et al
Journal of Translational Medicine 23 (149)
2025
https://doi.org/10.1186/s12967-025-06146-6
BIOMEDICAL RESEARCH>Clinical Assessment, Symptoms and Diagnosis
Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK
Mansoubi M, et al.
BMJ Open15 (e094658)
2025
https://doi.org/10.1136/bmjopen-2024-094658
Clinical Assessment, Symptoms and Diagnosis> NICE Guidelines
Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia
Davis, L et al
Frontiers in Neuroscience 19:1498981
2025
https://doi.org/10.3389/fnins.2025.1498981
BIOMEDICAL RESEARCH>Mitochondria and energy production
Using Single-Cell Raman Microspectroscopy to Profile Human Peripheral Blood Mononuclear Cells
Gan, E et al
Methods in Molecular Biology, vol 2920. Humana, New York, NY.
2025
https://doi.org/10.1007/978-1-0716-4498-0_3
BIOMEDICAL RESEARCH>Biomarker identification
Raman micro-spectroscopy as a tool to study immunometabolism
Xu J and Morten KJ
Biochemical Society Transactions 52 (2): 733–745
2024
https://doi.org/10.1042/BST20230794
BIOMEDICAL RESEARCH>Immunology>Metabolomics
Developing a blood cell-based diagnostic test for myalgic encephalomyelitis/chronic fatigue syndrome using peripheral blood mononuclear cells
Jiabao X et al
Advanced Science 10: 2302146
2023
https://doi.org/10.1002/advs.202302146
BIOMEDICAL RESEARCH>Biomarker identification
Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study
Clague-Baker et alFatigue: Biomedicine, Health & Behavior
2023
https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2245584
BIOMEDICAL RESEARCH>Post-exertional malaise (PEM)|PROGNOSIS AND QUALITY OF LIFE>Technology- Wearables and activity monitoring
Long COVID: mechanisms, risk factors and recovery
Astin, R et al.
Experimental Physiology 108: 12–27
2023
https://doi.org/10.1113/EP090802
LONG COVID (with links to ME/CFS)>Prognosis and quality of life
Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles.
González-Cebrián A, et al
Frontiers in Medicine 9:842991
2022
http://doi.org/10.3389/fmed.2022.842991
BIOMEDICAL RESEARCH>Biomarker identification>Extracellular vesicles>Gene Expression
Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome
Monzón-Nomdedeu MB, et al
World Journal of Stem Cells 13 (8): 1134-1150
2021
https://pubmed.ncbi.nlm.nih.gov/34567431/
BIOMEDICAL RESEARCH>Biomarker identification
Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients (On Behalf Of The European Network On Me/CFS Euromene)
Kujawki S et al
Journal of Clinical Medicine 10 (7): 1542
2021
https://pubmed.ncbi.nlm.nih.gov/33917586/
BIOMEDICAL RESEARCH>Mitochondria and energy production>Neurology: Autonomic nervous system (ANS) dysfunction
Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Almenar-Perez E, et al
Scientific Reports 10 (1): 2064
2020
https://www.ncbi.nlm.nih.gov/pubmed/32034172
BIOMEDICAL RESEARCH>Epigenetics
Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis
Słomko J et al
Journal of Clinical Medicine 9 (8)
2020
https://www.mdpi.com/2077-0383/9/8/2531
BIOMEDICAL RESEARCH>Neurology: Autonomic nervous system (ANS) dysfunction
Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects
Polli A, et al
Clinical Therapy 41 (4): 641-655
2019
https://doi.org/10.1016/j.clinthera.2018.12.012
BIOMEDICAL RESEARCH>Exercise physiology / testing
Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types
Tomas C et al
PeerJ 7: e6500
2019
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398432/
BIOMEDICAL RESEARCH>Mitochondria and energy production
Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test
Tomas, C et al
Scientific Reports 9: 11464
2019
https://doi.org/10.1038/s41598-019-47966-z
BIOMEDICAL RESEARCH>Mitochondria and energy production
The ‘Cognitive Behavioural Model’ of Chronic Fatigue Syndrome: Critique of a Flawed Model
Geraghty K and Adeniji C
Health Psychology Open
2019
https://doi.org/10.1177/2055102919838907
MANAGEMENT>Cognitive Behavioural Therapy (CBT)
Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys.
Geraghty K et al
Journal of Health Psychology 24 (10): 1318-1333
2019
https://www.ncbi.nlm.nih.gov/pubmed/28847166
MANAGEMENT>Exercise, Pacing and activity management
The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients
Zalewski P et al
Brain Science 10 (1): 4
2019
https://www.mdpi.com/2076-3425/10/1/4
MANAGEMENT>Exercise, Pacing and activity management
Impact of pharmacological agents on mitochondrial function: a growing opportunity?
Stoker, ML et al
Biochemistry Society Transactions 47 (6): 1757–1772
2019
https://doi.org/10.1042/BST20190280
MISCELLANEOUS|BIOMEDICAL RESEARCH>Mitochondria and energy production>Pharmacological treatment
A new approach to find biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) by single-cell Raman micro-spectroscopy
Xu J et al
RSC, Analyst, 144 (3): 913-920
2018
http://pubs.rsc.org/en/Content/ArticleLanding/2018/AN/C8AN01437J#!divAbstract
BIOMEDICAL RESEARCH>Phenotypes and sub-groups
Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter
Geraghty K and Blease C
Disability and Rehabilitation 21: 1-10.
2018
https://www.ncbi.nlm.nih.gov/pubmed/29929450
MANAGEMENT>Exercise, Pacing and activity management
Potential clinical usefulness of gut microbiome testing in a variety of clinical conditions
Morten, KJ et al
Human Microbiome Journal 10: 6-10
2018
https://doi.org/10.1016/j.humic.2018.08.003
BIOMEDICAL RESEARCH>Gastrointestinal and microbiome
Cellular Bioenergetics is Impaired in patients with Chronic Fatigue Syndrome
Tomas C et al
PLoS ONE 12(10)
2017
https://doi.org/10.1371/journal.pone.0186802
BIOMEDICAL RESEARCH>Metabolomics
Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome
Schoeman EM et al
MBC Medical Genetics 18: 29.
2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356238/
BIOMEDICAL RESEARCH>Mitochondria and energy production
The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People
Oosterwijck JV et al
Pain Physicians 20(3): E389-E399
2017
https://www.ncbi.nlm.nih.gov/pubmed/28339438
BIOMEDICAL RESEARCH>Neurology: Autonomic nervous system (ANS) dysfunction
The experience of sleep in chronic fatigue syndrome: A qualitative interview study with patients
Gotts ZM et al
British Journal of Health Psychology 21(1): 71-92
2016
https://www.ncbi.nlm.nih.gov/pubmed/25728396
BIOMEDICAL RESEARCH>Sleep disturbance
Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: case-control study
Jones DEJ et al
European Journal of Clinical Investigation 42(2): 186-194
2012
https://www.ncbi.nlm.nih.gov/pubmed/21749371
BIOMEDICAL RESEARCH>Muscle
A gene signature for post-infectious chronic fatigue syndrome
Gow JW, et al
BMC Medical Genomics 2: 38.
2009
https://bmcmedgenomics.biomedcentral.com/articles/10.1186/1755-8794-2-38
BIOMEDICAL RESEARCH>Gene Expression
Risk factors for severe ME/CFS
Pheby D and Saffron L
Biology and Medicine 1(4): 50-74
2009
http://www.meassociation.org.uk/wp-content/uploads/2013/04/Biology-and-Medicine_Published-paper_vol1_4_50-74.pdf
PROGNOSIS AND QUALITY OF LIFE>Severe ME
Dietary intervention in chronic fatigue syndrome
Hobday RA et al
Journal of Human Nutrition and Dietetics 21(2): 141-149
2008
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-277X.2008.00857.x/abstract
MANAGEMENT>Diet and nutrition
The Role of Cytokines in Muscle Fatigue in Patients with Chronic Fatigue Syndrome (CFS)
Anne McArdle et al
The Faseb Journal
2007
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.29.1_supplement.1055.34
BIOMEDICAL RESEARCH>Immunology
CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological artefacts
Chalmers RA et al
Clinica Chimica Acta 364(1-2): 148-158
2006
https://www.ncbi.nlm.nih.gov/pubmed/16095585
CLINICAL ASSESSMENT, SYMPTOMS AND DIAGNOSIS>Investigations
Urinary and plasma organic acids and amino acids in chronic fatigue syndrome
Jones MG et al
Clinica Chimica Acta 361(1-2): 150-158
2005
https://www.ncbi.nlm.nih.gov/pubmed/15992788
CLINICAL ASSESSMENT, SYMPTOMS AND DIAGNOSIS>Investigations
Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome
Jones MG et al
Clinica Chimica Acta 360(1-2): 173-177
2005
https://www.ncbi.nlm.nih.gov/pubmed/15967423
CLINICAL ASSESSMENT, SYMPTOMS AND DIAGNOSIS>Pharmacological treatment
Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome.
Chaudhuri A et al
NeuroReport 14(2): 225-228.
2003
https://www.ncbi.nlm.nih.gov/pubmed/12598734
BIOMEDICAL RESEARCH>Neurology: Central nervous system and neuroimaging
Chronic fatigue syndrome: new evidence for a central fatigue disorder
Georgiades E et al
Clinical Science 105(2): 213-218
2003
https://www.ncbi.nlm.nih.gov/pubmed/12708966
BIOMEDICAL RESEARCH>Neurology: Neurotransmitter function
Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome
Khan F et al
Clinical Physiology and Functional Imaging 23(5): 282-285
2003
https://www.ncbi.nlm.nih.gov/pubmed/12950326
BIOMEDICAL RESEARCH>Neurology: Neurotransmitter function
Antiviral Pathway Activation in Patients with Chronic Fatigue Syndrome and Acute Infection
Gow JW, et al
Clinical Infectious Diseases 33(12): 2080-2081
2001
https://academic.oup.com/cid/article/33/12/2080/366051
BIOMEDICAL RESEARCH>Infection