"Treatment targets" is a phrase that comes up a lot on ME/CFS research.

What does this mean, exactly?

A treatment target something in the biology of an illness that a treatment or therapy can act on. It could be a receptor, immune pathway, autoantibody, virus, metabolic pathway, blood-flow problem, nervous-system abnormality, inflammatory signal, or cell type.

In other words, it's something that researchers can target and modify in some way as to lessen the impact of or completely erradicate symptoms or disease process.

Here's what the process of identifying treatment targets and developing therapies usually looks like:

1. It all starts in the research lab - researchers look for biological patterns seen in the patient population that stand out from the control population. This can be anything including genetic signals, inflammation, immune abnormalities, metabolite abnormalities or unusual blood flow.
2. Find out whether the pattern is part of the disease biology. Just because a pattern is found does not mean that it's driving the illness, so further research must be carried out to determine if it is causative.
3. They narrow down the biological pattern findings to specific target(s). These can be a metabolic pathways, cell types, autoantibodies, inflammatory signals or viral responses.
4. They look for a drug or treatment that can affect that target(s). Repurposed drugs that already have FDA approval are attractive because they can be made available to patients much sooner than developing a new drug from scratch. Examples of this are Low-Dose Naltrexone, Pyridostigmine and Low-Dose Rapamycin.
5. They perform clinical trials around the treatement and target to see if it actually works. They also assess treatment safety. After all a treatment is only viable if is improves symptoms and is safe to use.

This is why studies such as DecodeME, SequenceME and Selin/Gil/Kumar immune profiling are so important.

For example, DecodeME uses GWAS to look for genetic signals that are more common in people with ME/CFS than in controls. Those signals are not treatments by themselves, but they can point researchers toward biological pathways that may be involved in the disease.

SequenceME goes deeper by using long-read whole-genome sequencing. The goal is to find rare variants, structural DNA changes and other genetic patterns that DecodeME could not see. That could help researchers identify biological subtypes, disease mechanisms and eventually possible treatment targets.

Selin / Gil / Kumar immune profiling is looking at immune dysfunction, including T-cell exhaustion, unusual CD4+/CD8+ T-cell populations, viral or autoimmune targets and immune-defined patient subgroups. If researchers can identify what the immune system is reacting to, that could point toward more specific treatments: antiviral, immune-modulating, autoimmune-targeted or something else.

So the flow is essentially:

we found something abnormal >
we understand what this abnormally is doing >
we think we can change it with this drug >
let's test it and see if it helps patients

But funding might be the biggest bottleneck of all.

Research, clinical trial design, participant recruitment, data analysis, biomarker validation, and follow-up studies all require a lot of money - and ME/CFS research has been criminally underfunded for decades.

There are some encouraging signs. The UK government recently provided £4.75 million for SequenceME to begin long-read whole-genome sequencing of 6,000 DecodeME samples. Germany has also announced a major “National Decade Against Post-Infectious Diseases,” with €500 million planned over 10 years for research into post-infectious diseases including ME/CFS and Long Covid.

That is the kind of scale we need more of.

I’d love to hear others’ thoughts:

What studies or trials do you think are most likely to move us toward real treatments?

And maybe the biggest question: how do we secure more serious funding for ME/CFS research?

sources:
https://toolkit.ncats.nih.gov/module/getting-started/understand-the-rd-process/discovery-of-therapeutic-approach/

https://magazine.hms.harvard.edu/articles/tracing-path-basic-research-transformative-therapies

https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process

https://www.meresearch.org.uk/decodeme-initial-results-published/

https://megenetics.org.uk/our-projects/sequence-me-long-covid/

https://solvecfs.org/research-and-registry/ramsay-research-grants/meet-the-researchers/liisa-selin-and-anna-gil/

I wanted to start a living list of current or recent ME/CFS research initiatives that seem worth following, all in one central place.

I'm sure there are more studies that should be included here. Please add any studies, trials, labs, or research groups that we should add in the comments.

The goal is to have one thread where patients, caregivers, and interested clinicians can get a quick sense of what is actually happening in ME/CFS research right now.

Genetics / genomics

DecodeME

start date: September 2022
end date: August 2025

The largest ME/CFS genetic study to date. DecodeME aimed to find genetic causes of why people become ill with Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS). The study will help us understand the disease and ultimately find treatments. Initial results identified eight genetic signals associated with ME/CFS risk.

https://institute-genetics-cancer.ed.ac.uk/decodeme

SequenceME / Sequence ME & Long Covid

start date: mid 2026
end date (planned): April 2027

A major whole-genome sequencing project building on DecodeME, led by Action for ME, the University of Edinburgh, Oxford Nanopore Technologies, and EMBL-EBI. The full proposed study aims to use long-read sequencing to analyze up to 9,000 people with ME/CFS and 9,000 with Long Covid, looking for rare variants, structural DNA changes, biological subtypes, and shared or distinct disease mechanisms. Early phases have now received $4.75 million in funding from the UK government to begin sequencing 6,000 DecodeME ME/CFS samples, while additional funding is still needed for later phases and the Long Covid arm.

https://megenetics.org.uk/our-projects/sequence-me-long-covid/

Treatment / clinical trials

LIFT trial

start date: September 10, 2024
end date (planned): September 2026

LDN + Mestinon/pyridostigmine, separately and together, in ME/CFS patients with orthostatic intolerance.

https://www.omf.ngo/the-life-improvement-trial/

Rapamycin / sirolimus for ME/CFS and related conditions

start date: December 2023
end date: July 2027

An observational study looking at whether low-dose sirolimus/rapamycin reduces symptom burden and improves quality of life, while also measuring whether it changes mTOR-related autophagy dysfunction in a subset of patients. Participants complete symptom and quality-of-life questionnaires, with blood samples collected before and during treatment to track autophagy-related biomarkers.

https://clinicaltrials.gov/study/NCT06257420

Charité / NKSG treatment studies

Charité / NKSG

German clinical study group running treatment studies for ME/CFS and post-COVID syndrome, including immune/autonomic/vascular approaches.

IA-PACS-CFS / immunoadsorption

A double-blind, randomized, sham-controlled trial investigating immunoadsorption (a blood-filtering treatment to remove autoantibodies) for ME/CFS and post-COVID ME/CFS patients.

https://cfc.charite.de/en/clinical_research/nksg/trial_ia_pacs_cfs

Repeat immunoadsorption in Post-COVID ME/CFS

A Charité/NKSG observational study testing whether removing ß2-adrenergic receptor autoantibodies through immunoadsorption can improve symptoms in Post-COVID ME/CFS patients. Earlier small studies reportedly found rapid improvement in some patients, and this study is looking at whether repeat treatment can produce longer-term benefit.

https://cfc.charite.de/en/clinical_research/nksg/trial_ria

PoCoVIT / methylprednisolone for Post-COVID cognitive symptoms

A Charité/NKSG randomized placebo-controlled study testing whether methylprednisolone can improve cognitive symptoms in Post-COVID Syndrome. The trial is based on the idea that persistent inflammation in the central nervous system may contribute to brain fog, and that a short steroid course could reduce this inflammation and improve memory/cognitive function.

https://cfc.charite.de/en/clinical_research/nksg/trial_pocovit/

VERI-LONG / vericiguat for Post-COVID fatigue and exercise intolerance

A Charité/NKSG Phase 2a placebo-controlled trial testing whether vericiguat can improve physical function in Post-COVID Syndrome patients with severe fatigue and exercise intolerance. The idea is that inflammation-related blood-flow problems may contribute to symptoms, and vericiguat may help by dilating blood vessels and improving vascular/organ blood flow.

https://cfc.charite.de/en/clinical_research/nksg/trial_veri_long

HBOT for Post-COVID Syndrome and ME/CFS

A Charité/NKSG observational study testing whether hyperbaric oxygen therapy can improve physical function in Post-COVID Syndrome and ME/CFS. HBOT is being studied because it may improve circulation, support capillary formation, and affect immune function; earlier studies suggested benefits for neurocognitive symptoms in Post-COVID patients.

https://cfc.charite.de/en/clinical_research/nksg/trial_hbot

Immune dysfunction / T-cell research

Selin / Gil / Kumar — T-cell exhaustion and immune profiling

Researchers at UMass Chan Medical School, including Dr. Liisa Selin and Dr. Anna Gil, along with collaborators such as Dr. Roshan Kumar at HiFiBiO Therapeutics, are studying immune dysfunction in ME/CFS and Long Covid. Their work focuses on abnormal T-cell patterns, including increased rare CD4+/CD8+ “double positive” T cells, altered CD4:CD8 ratios, signs of CD8 T-cell exhaustion, and unusual immune responses to persistent viruses such as EBV, CMV, VZV, and HHV-6. The goal is to identify immune biomarkers, patient subgroups, and possible viral or autoimmune targets that could eventually guide diagnosis and treatment.

Altered T Cell Responses in ME/CFS

funder: NIH / NIAID
grant: R01 AI159314

NIH-funded UMass Chan study examining whether ME/CFS involves chronic immune dysregulation, including exhausted CD8 T cells, unusual CD4+/CD8+ T-cell populations, altered EBV-specific responses, and T-cell receptor patterns that may point to persistent viral or autoimmune triggers.

Altered T Cell Responses in Long Covid and ME/CFS

funder: Patient-Led Research Collaborative
year: 2023

Patient-Led Research Collaborative-funded project studying whether Long Covid and ME/CFS share a common pattern of immune dysfunction after infection, especially CD8 T-cell exhaustion and possible herpesvirus reactivation.

Immune Repertoire Profiling of Long Covid and ME/CFS

funder: Patient-Led Research Collaborative
year: 2024
collaborators: Selin Lab, HiFiBiO Therapeutics, Dr. Roshan Kumar

A 2024 collaborative project between PLRC, HiFiBiO Therapeutics, and the Selin Lab using single-cell immune profiling to identify what B cells and T cells are reacting to in ME/CFS and Long Covid. The goal is to find viral or autoimmune targets, define patient subgroups, and move toward biomarkers or precision treatments.

Solve M.E. Ramsay Award: Altered T Cells in ME/CFS

funder: Solve M.E.
year: 2020

Earlier seed funding that helped support the Selin/Gil work on abnormal T-cell responses in ME/CFS, including the hypothesis that an infection-triggered immune response may lead to long-term immune dysfunction.

Jarred Younger / Neuroinflammation, Pain and Fatigue Laboratory

Dr. Jarred Younger’s lab at the University of Alabama at Birmingham studies neuroinflammation, pain, fatigue, and related mechanisms in conditions including ME/CFS and fibromyalgia. His ME/CFS brain imaging work has used magnetic resonance spectroscopy to look for metabolite, lactate, temperature, and other abnormalities consistent with low-level neuroinflammation across multiple brain regions.

https://solvecfs.org/research-and-registry/ramsay-research-grants/meet-the-researchers/jarred-younger/

Whole-brain MRS study in ME/CFS

study: Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome
PI: Jarred Younger, PhD

A neuroimaging study using whole-brain magnetic resonance spectroscopy found widespread metabolite and temperature abnormalities in ME/CFS patients compared with healthy controls. Findings included elevated choline, increased lactate in several brain regions, and higher brain temperature in some areas, supporting the hypothesis that low-level neuroinflammation may be involved in ME/CFS.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6612467/

Low-dose naltrexone / inflammatory cytokines in fibromyalgia

Dr. Younger has also studied low-dose naltrexone in fibromyalgia, a related chronic pain and fatigue condition. His work suggests that LDN may reduce pro-inflammatory cytokines over time and is associated with symptom improvement in some fibromyalgia patients, helping build interest in LDN as a possible immune-modulating treatment relevant to ME/CFS and overlapping conditions.

https://pubmed.ncbi.nlm.nih.gov/28536359/

Stanford ME/CFS research

Stanford ME/CFS Initiative

Stanford’s ME/CFS Initiative is conducting clinical research focused on improving diagnosis and treatment of ME/CFS. Current work includes brain imaging studies, PET/MRI studies looking for inflammation in the brain and body, and a serum biomarker study for ME/CFS and Long Covid.

https://med.stanford.edu/chronicfatiguesyndrome/research.html

MRI / PET-MRI studies at Stanford

Stanford is recruiting for imaging studies in ME/CFS, including brain MRI to look for anatomical changes and PET/MRI scans to look for inflammation in the brain and body of moderate-to-severe ME/CFS patients.

https://med.stanford.edu/chronicfatiguesyndrome/research.html

Stanford serum biomarker study

A Stanford study looking for potential serum biomarkers for ME/CFS and Long Covid. The goal is to identify measurable blood-based signals that could help with diagnosis or disease understanding.

https://med.stanford.edu/chronicfatiguesyndrome/research.html

Stanford ME/CFS Collaborative Research Center / Ron Davis

The Stanford ME/CFS Collaborative Research Center, directed by Dr. Ronald W. Davis and supported by Open Medicine Foundation, is focused on mechanistic and diagnostic research in ME/CFS and Long Covid. Active projects include work on saliva-based diagnostics, pathogen detection, mitochondrial dysfunction, neutrophil dysfunction, viral risk factors, PEM/crash biology, red blood cell deformability, and BH4/nitric oxide biology.

https://www.omf.ngo/collaborative-research-center-stanford/

Itaconate shunt / mitochondrial dysfunction

A Stanford/OMF project investigating whether the “itaconate shunt” may contribute to mitochondrial dysfunction and energy impairment in ME/CFS. The work looks at mitochondrial function in immune cells and related metabolic pathways that could help explain fatigue, PEM, and impaired cellular energy production.

https://www.omf.ngo/collaborative-research-center-stanford/

Pathogens, viral risk factors, and immune activation

Stanford/OMF researchers are also studying whether viruses, parasites, bacteria, or viral risk factors may be involved in ME/CFS, Long Covid, and related conditions. This includes work looking at immune responses, inflammation, and possible infectious contributors.

https://www.omf.ngo/collaborative-research-center-stanford/

Red blood cells, neutrophils, and BH4 / nitric oxide biology

Several Stanford/OMF projects are looking at possible blood, immune, and vascular mechanisms in ME/CFS. These include red blood cell deformability, neutrophil dysfunction, and BH4/nitric oxide biology, all of which may be relevant to circulation, immune function, and cellular energy problems.

INIM / Nova Southeastern University

Institute for Neuro-Immune Medicine / Nancy Klimas

The Institute for Neuro-Immune Medicine at Nova Southeastern University is actively researching ME/CFS, including clinical immunology, clinical systems biology, genomics, neuroinflammation, and related post-viral illness mechanisms. Their ME/CFS research includes collaborations with institutions such as the CDC, Miami VA, NIH, and private entities.

https://www.nova.edu/inim/research-studies/me-cfs.html

Directed probiotics in ME/CFS

A Nova Southeastern / INIM study testing whether the probiotic Floradapt Intensive GI, also known as i3.1, can reduce GI inflammation, normalize gut health, and potentially improve broader symptoms in ME/CFS. The study includes ME/CFS patients with or without IBS.

https://clinicaltrials.gov/study/NCT06211062

Microbiota dysbiosis and oxidative stress in Post-COVID sequelae and ME/CFS

An INIM pilot study looking at overlap between Post-COVID Syndrome and ME/CFS, including microbiome changes, oxidative stress, nutritional status, and immune markers. The study is based on the idea that post-viral fatigue and ME/CFS may involve interconnected changes in microbial and antioxidant defense systems.

RECOVER / Long Covid research relevant to ME/CFS overlap

RECOVER Initiative

The NIH RECOVER Initiative is a large national research program studying Long Covid causes, diagnosis, phenotypes, and treatments. It is relevant to ME/CFS because many Long Covid patients have overlapping symptoms, including post-exertional malaise, fatigue, cognitive dysfunction, orthostatic intolerance, dysautonomia, and unrefreshing sleep.

https://recovercovid.org

RECOVER adult cohort: post-COVID ME/CFS

A 2025 RECOVER adult observational cohort study found that 4.5% of post-COVID participants met ME/CFS diagnostic criteria, compared with 0.6% of participants without SARS-CoV-2 infection. The study also found that new ME/CFS cases after COVID were much higher than pre-pandemic estimates, with PEM, orthostatic intolerance, and cognitive impairment among the most commonly reported symptoms.

https://recovercovid.org/news/nih-funded-study-finds-cases-mecfs-increase-following-covid-19

RECOVER-ENERGIZE / PEM and exercise intolerance

A RECOVER clinical trial platform focused on exercise intolerance and post-exertional malaise after COVID. It includes separate approaches for people with exercise intolerance and people with PEM, with the PEM arm focused on structured pacing rather than exercise-based rehabilitation.

https://trials.recovercovid.org/ENERGIZE

RECOVER-AUTONOMIC / dysautonomia and POTS

A RECOVER clinical trial focused on Long Covid-related autonomic dysfunction, including POTS-like symptoms such as fast heart rate, dizziness, fatigue, and other symptoms that worsen when standing. The study is testing approaches including IVIG, ivabradine, and coordinated non-drug measures such as diet changes and compression.

https://trials.recovercovid.org/autonomic

RECOVER-SLEEP / sleep disturbance

A RECOVER clinical trial platform focused on sleep problems after COVID, including hypersomnia, sleep-wake rhythm problems, and other sleep disturbances. This is relevant to ME/CFS overlap because unrefreshing sleep and disrupted sleep are core problems for many patients.

https://trials.recovercovid.org/SLEEP

RECOVER-TLC / Long Covid treatment trials

RECOVER-TLC is the next phase of RECOVER treatment trials. One current study, REVERSE-LC, is testing baricitinib, a JAK/STAT inhibitor, for Long Covid-related cognitive problems, fatigue, heart/lung function, and quality of life. Other RECOVER-TLC treatment ideas have included low-dose naltrexone and other immune or symptom-targeted approaches.

https://recovercovid.org/news/recover-tlc-opens-expanded-enrollment-reverse-lc-clinical-trial

The purpose of the LIFT trial is to better understand te effects of 2 drugs in ME/CFS patients: Low-Dose Naltrexone (LDN) and Pyridostigmine (Mestinon).

Pyridostigmine (Mestinon) is an acetylcholinesterase inhibitor used off-label for ME/CFS to treat orthostatic intolerance, reduce exertional fatigue, and improve aerobic capacity. Research indicates it works by boosting acetylcholine levels, improving cardiac output, and enhancing parasympathetic tone.

Low-dose naltrexone (LDN) is an off-label medication (typically 1.5 mg to 4.5 mg) used to modulate the immune system and reduce chronic pain or inflammation.

Patients enrolled in the trial must meet the following criteria:

• aged 18-65
• meet the Canadian consensus criteria (CCC) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
• have Orthostatic Intoleranc

Trial process:
The trial enrolled 160 participants, randomly assigned to one of four groups:

• LDN + Mestinon
• LDN + placebo
• Mestinon + placebo
• placebo + placebo

Doses are gradually increased, with Mestinon titrated from 30 mg to 60 mg three times daily and LDN from 1.5 mg to 4.5 mg once daily. Participants can reduce the dose if they have trouble tolerating it. The trial lasts about three months per participant and includes three in-person visits, four virtual visits, questionnaires, blood and urine collection, and two submaximal cardiopulmonary exercise tests.

Objectives:
The objective of the study is not only to determine the effectiveness of these drugs on ME/CFS patients but also to gain insights into the illnesses pathogenesis.

This trial could also help better understand potential ME/CFS biomarkers and subtypes.

Finally, it could enable the widespread use of Pyridostigmine and LDN by primary care doctors - if deemed safe and effective.

The trial began September 10, 2024 and is scheduled to end September 2026. I believe the completion / results are estimated to be published by November 2026.

Lead investigators:
David Systrom, MD
Jonas Bergquist, MD/PhD
Donna Felsenstein, MD
Wenzhong Xiao, PhD

Location:
Brigham and Women's Hospital (BWH) of Harvard Medical School

Thoughts:
I've personally experienced some improvement while taking both of these drugs. Although I can't be 100% sure how effective they have been, I did experience a sustained 9 month period of improvement that started weeks after starting LDN (I take Pyridostigmine only as needed - not regularly).

I did not experience any side effects other than vivid dreams the first 2 nights of LDN. Then it went away.

Curious if anyone here has tried LDN, Mestinon, or both.

• What dose did you start at?
• Did you have to titrate slowly?
• Did it help with PEM, pain, orthostatic intolerance, sleep, brain fog, flu-like symptoms, or overall baseline?
• Any side effects or worsening at first?
• Or did it do nothing?

Not medical advice - just interested in people's real-world experiences while we wait for better trial data.

Sources / for more info:
https://www.omf.ngo/the-life-improvement-trial/
https://clinicaltrials.gov/study/NCT06366724

I wanted to start a discussion about meditation, yoga nidra, breathwork, and other nervous-system support tools in ME/CFS and get a sense of what has worked for folks, if any.

I'm not talking about expensive recovery programs with slick marketing, over-promising guaranteed cures. I'm talking about nuts-and-bolts meditaton and relaxation techniques that anyone can do for free.

One reason this might be at least plausible is that the HPA axis - one of the body’s main stress-response systems - has come up repeatedly in ME/CFS research. There was also a recent IACFS/ME talk by Dr. da Silva discussing HPA-axis findings in ME/CFS brain autopsy tissue. As summarized by Health Rising, the talk reportedly found major abnormalities in the hypothalamus/pituitary side of the HPA axis in a small group of ME/CFS donors, including a striking reduction in CRH-producing neurons. That is early/preliminary, but still interesting.

To me, that points to a middle position:

Maybe practices like meditation or yoga nidra can help some people with things like sleep, stress load, hyperarousal, adrenaline feelings, sensory overload, or coping with PEM fear.

ME/CFS aside - the health benefits of meditation and similar stress reduction techniques have been known for millenia.

But that is very different from saying they cure ME/CFS.

If ME/CFS involves immune dysfunction, autonomic dysfunction, metabolism, PEM biology, sleep disruption, brain changes, and possibly HPA-axis dysfunction, as research points to, and the initial insult came from a viral infection, as many report, then nervous-system calming tools might help to a degree without being a complete answer.

sources:
https://pubmed.ncbi.nlm.nih.gov/21946893/
https://meassociation.org.uk/medical-matters/items/stress-and-me-cfs/
https://www.healthrising.org/blog/2025/12/04/chronic-fatigue-hpa-axis-autopsy/
https://www.meresearch.org.uk/chronic-stress-and-brain-fog-in-me-cfs-more-evidence-for-dysfunction-of-the-hypothalamic-pituitary-adrenal-hpa-axis-in-me-cfs/

hey guys, I just released a new album of some instrumental material I've been working on the last two years. inspired by Dungen, Bo Hansson, Boards of Canada, MBV and others.

Thanks for the listen, if interested!
https://ektachromemusic.bandcamp.com/album/psychic-readings