Interviews & Insights
Scientific interviews, paper reviews and experience reports – curated summaries from the ME/CFS and PVFS research world.
Note: These contents are personal experience reports and scientific assessments – not medical recommendations. Every person with ME/CFS is different.
GLP-1 Agonists (Semaglutide/Ozempic) as a New Therapeutic Option in ME/CFS
Prof. Carmen Scheibenbogen (Charité Berlin)
Prof. Carmen Scheibenbogen from the Charité Berlin presents the scientific basis for the use of GLP-1 agonists such as semaglutide (Ozempic/Wegovy) in ME/CFS. The medications address several known ME/CFS mechanisms simultaneously, and a clinical trial is already underway at the Charité.
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Why GLP-1 agonists are interesting in ME/CFS
GLP-1 agonists have anti-inflammatory effects, improve endothelial function and capillary blood flow, and correct impaired glucose utilization – all mechanisms that are demonstrably dysregulated in ME/CFS.
Existing evidence from other diseases
47 MCAS patients who received GLP-1 agonists reported improvements in fatigue, brain fog, and pain. A fibromyalgia study showed reduced fatigue and inflammatory markers. No ME/CFS-specific studies have been published yet.
Charité study with semaglutide is underway
Observational study with ME/CFS patients according to Canadian Consensus Criteria, Bell Score 30-60. Starting dose 0.25mg weekly. Primary goal: improvement of physical function measured with SF-36 and Fitbit. Results expected in approximately 1 year.
Two US studies in preparation
Scripps study: 1,000 long COVID patients with tirzepatide (dual GLP-1/GIP agonist), placebo-controlled, remote participation also possible. RECOVER study also in preparation.
Subgroups and Caution
Dr. David Kaufman (USA) is already treating ME/CFS patients with microdosing (1/10 of the standard dose) and reports positive results even in patients with normal BMI. Caution is advised in cases of underweight and very severe ME/CFS.
Germany: Half-billion investment in post-infectious diseases
Germany is planning the National Decade against post-infectious diseases – 500 million euros for research over 10 years. At the same time, the Federal Joint Committee has approved the reimbursement of three off-label medications for Long COVID.
Key Learnings
- →GLP-1 agonists simultaneously address neuroinflammation, endothelial dysfunction, and glucose metabolism
- →Charité study with semaglutide is underway – results in approximately one year
- →Microdosing (1/10 standard dose) could be effective – experiences from US practice
- →Not for underweight individuals or very severe ME/CFS without more experience data
- →Germany invests 500 million euros in post-infectious diseases
- →ME/CFS has at least three biological subgroups: autoimmune, inflammatory, metabolic
Read full summary ↓
Prof. Carmen Scheibenbogen from the Charité Berlin presents GLP-1 agonists such as semaglutide as a promising new treatment option. The rationale: GLP-1 agonists have anti-inflammatory effects, improve endothelial function, capillary blood flow, and impaired glucose metabolism – all mechanisms that have been demonstrably dysregulated in ME/CFS. Initial positive signals are emerging from MCAS and fibromyalgia studies. An observational study with semaglutide is currently underway at the Charité, with results expected in approximately one year. In the United States, Dr. David Kaufman is already treating ME/CFS patients with microdosing and reports positive outcomes. Two US studies are in preparation, including a large Scripps study involving 1,000 patients. Germany is investing 500 million euros in the National Decade against post-infectious diseases.
Amatica: Patient-led RNA sequencing to decipher ME/CFS subgroups
Nick & Jack (Amatica) – Interview mit Cort Johnson (Health Rising)
Two ME/CFS patients with a scientific background – a former CSO of a biotech company and an aerospace engineer – have founded Amatica: a patient-led initiative that uses RNA sequencing of all 20,000 genes to identify ME/CFS subgroups and enable treatment predictions.
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The core problem: Treatment Roulette
A patient improves with a medication – nine others experience no effect, one deteriorates permanently. This is due to the extreme heterogeneity of ME/CFS. Amatica aims to solve this through subgroup identification.
RNA sequencing of all 20,000 genes
From a blood sample, the expression of all genes is measured. This shows which genes are active or inactive, which immune states are activated, and which signaling pathways are dysregulated. The deepest possible biological insight from blood.
350-question questionnaire as the decisive layer
Not only biology – also deep phenotyping. Symptoms in detail, treatment responses in clinical format (baseline, 1 week, 1 month, 3 months, 6 months). This allows correlation between biology and clinical reality.
Currently 300 patients – one of the largest RNA studies in ME/CFS
The average study in ME/CFS has 42 participants. Amatica is already larger than 95-99% of all ME/CFS studies. At 300, already more detailed phenotyping than ever before in an RNA dataset.
Lifelong updates at no additional cost
Anyone who submits a sample once will automatically receive new insights with every dataset growth. At 300, 500, 1,000, and 10,000 patients, the profile of each participant will be re-analyzed and updated.
PEM study planned: Samples before and after a crash
First patients have already voluntarily sent in samples following naturally triggered PEM – the blood values were massively different. A dedicated PEM study with samples before and after crash is planned.
Key Learnings
- →ME/CFS is probably 10-100 different diseases – subgroup identification is crucial
- →RNA sequencing of all genes is the most unbiased way to develop treatment predictions
- →Patient-led research with a direct personal stake in life may be more effective than standard academic research
- →Every crash leaves measurably different blood values – PEM is biologically demonstrable
- →Amatica offers lifelong updates – a one-time sample, continuously new findings
- →Clinical network with physicians is the fastest path to treatment impact
Read full summary ↓
Nick and Jack – both personally affected by ME/CFS and Long COVID respectively – founded Amatica with the goal of biologically decoding the extreme differences between patients. Nick was CSO of a biotechnology company in Japan, Jack an aerospace engineer. Both fell ill in 2021. The core idea: every clinical trial fails because it treats 3-5 biologically completely distinct diseases as one. RNA sequencing of all 20,000 genes from blood, combined with a 350-question questionnaire, is intended to identify subgroups and enable treatment predictions. Currently 300 participants – one of the largest ME/CFS RNA datasets worldwide. Those who participate receive free lifetime updates as the dataset grows. A PEM study with samples taken before and after a crash is planned. Cost approximately 1,000 USD for RNA sequencing.
Itaconate Shunt and Oxygen Supply: Ron Davis & David Systrom on ME/CFS Mechanisms
Prof. Ron Davis (Stanford), Prof. David Systrom (Harvard)
Two of the world's leading ME/CFS researchers discuss their core hypotheses: Ron Davis is working on the itaconate shunt as a central energy disruption mechanism, David Systrom is investigating oxygen supply to the muscles during exertion. Both hypotheses complement each other and point to mitochondrial dysfunction as a common denominator.
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The Itaconate Shunt – Ron Davis Core Hypothesis
The itaconate shunt is a natural mechanism that is activated during infections and causes fatigue. In ME/CFS, it appears to remain permanently switched on. It diverts metabolites from the citric acid cycle – the main pathway of energy production – thereby reducing ATP production.
Oxidative Damage as a Source of Symptoms
ME/CFS patients show massive oxidative damage to metabolites. Example: Cysteine is oxidized to sulfate – it can then no longer be used and causes headaches. Vitamin C appears to have helped Ron Davis's son.
Zebrafish model: Switching the itaconate shunt on and off
In the zebrafish model, the itaconate shunt can be activated – the fish swim more slowly. A chemical compound that inhibits it allows them to swim normally again. Not a medication for humans, but a proof of concept.
Oxygen Supply to the Muscles – David Systrom
90%+ of the examined ME/CFS patients have preload insufficiency: The veins are not sufficiently contracted under exertion to efficiently pump blood back to the heart. Additionally, the increased cardiac output is not correctly directed to the working muscles.
Double hit in the musculature
Muscle biopsies show: fewer mitochondria than in healthy individuals plus additional dysfunction of the electron transport chain. Two independent problems that together lead to massively reduced energy production under exertion.
LIFT Study: Pyridostigmine + Low-Dose Naltrexone
Clinical trial tests Mestinon (improves vascular tone, helps with dysautonomia) alone and in combination with low-dose naltrexone (anti-inflammatory). With comprehensive biomarker profiling to identify subgroups that respond.
Key Learnings
- →The itaconate shunt could be the key mechanism that maintains ME/CFS after an infection
- →Over 90% of the examined ME/CFS patients have preload insufficiency – the oxygen supply is structurally impaired
- →Muscle biopsies show double hit: fewer mitochondria plus electron transport chain dysfunction
- →Oxidative damage could be directly responsible for many symptoms
- →Mestinon and low-dose naltrexone are being tested in combination in a clinical trial
- →Modeling (as in engineering) is crucial to understand the complexity of the mechanisms
Read full summary ↓
Ron Davis (Stanford) and David Systrom (Harvard) discuss their complementary hypotheses on ME/CFS. Davis focuses on the itaconate shunt – a mechanism that is activated during infections and diverts metabolites away from energy metabolism. In ME/CFS, it appears to remain permanently activated and reduces ATP production. Additionally, patients show massive oxidative damage. In the zebrafish model, the shunt can be activated and subsequently inhibited again by a chemical compound. Systrom investigates oxygen supply using invasive cardiopulmonary exercise testing: over 90% of patients have preload insufficiency – the veins do not collapse sufficiently during exertion. Additionally, blood is not correctly directed to the working musculature. Muscle biopsies reveal a double hit: reduced mitochondrial count plus dysfunction of the electron transport chain. The LIFT study tests mestinon and low-dose naltrexone alone and in combination, with extensive biomarker profiling.
ME/CFS Blood Test with 96% Accuracy – The EpiSwitch CFS Diagnosis
Prof. Dmitri Pshevski (Univ. East Anglia), Dr. Alexandre Akoulitchev (Oxford Biodynamics)
Oxford Biodynamics has developed a blood test in collaboration with the University of East Anglia that diagnoses ME/CFS with 96% accuracy. The technology uses 3D genomics – the spatial folding of DNA in blood cells – and identifies a unique biological pattern that only occurs in ME/CFS patients.
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The fundamental problem: No objective diagnosis
So far, ME/CFS could only be determined by exclusion diagnosis – often after years of waiting. All standard blood values are normal. This test could reduce the diagnosis time from years to weeks.
3D Genomics as a Key Technology
DNA is not linear but three-dimensionally folded – like origami. This folding determines which genes are active. The EpiSwitch test takes a snapshot of 1 million DNA folds and identifies a pattern specific to ME/CFS.
96% accuracy in the blind study
47 severe ME/CFS patients were compared with 61 healthy controls. The model was able to identify ME/CFS with 96% overall accuracy in a blind study. Published in the Journal of Translational Medicine, October 2025.
ME/CFS is a complex biological disorder – proven
The 200 identified markers show a network of dysregulated signaling pathways – not a single cause. This is the scientific proof that ME/CFS is a real biological disease.
Drug Repurposing from the Markers
Many of the identified signaling pathways already have approved medications. Copaxone (multiple sclerosis) and Rituximab (autoimmune) show overlaps with the ME/CFS markers – possible repurposing candidates.
Clinical availability coming soon
Oxford Biodynamics has a UKAS-accredited laboratory in Oxford. The test is expected to enter the clinic within months, not years. Similar to their prostate cancer test, which was available within months of validation.
Key Learnings
- →First objective blood test for ME/CFS with 96% accuracy – no more exclusion procedure necessary
- →ME/CFS has a biological fingerprint in the 3D structure of DNA in blood cells
- →The identified signaling pathways are druggable – existing medications could be repurposed
- →Diagnosis time could drop from years to weeks
- →Test works with simple blood draw
Read full summary ↓
The team from Oxford Biodynamics and the University of East Anglia has developed a revolutionary blood test for ME/CFS. The EpiSwitch CFS technology utilizes 3D genomics: DNA is folded three-dimensionally within cells, and this folding determines which genes are active or inactive. ME/CFS patients display a unique pattern of these folds that clearly distinguishes them from healthy controls. In a blind study involving 47 severe ME/CFS patients and 61 controls, an accuracy of 96% was achieved. The 200 identified markers reveal a network of dysregulated signaling pathways – not a single gene, but a complex biological system. Many of these signaling pathways already have approved medications, which enables drug repurposing. The test is expected to become clinically available in Oxford in the near future.
What Treatments Work Best for ME/CFS & Long COVID? – 3,925 Patients Report
Dr. Jarred Younger
A new peer-reviewed study surveyed nearly 4,000 affected individuals about more than 150 treatments for ME/CFS and Long COVID. The result: a prioritized list of the most effective therapies – rated according to positive and negative responses. At the very bottom: Graded Exercise Therapy as the only treatment with a negative overall score.
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Study size and methodology
1,759 people with ME/CFS and 1,376 people with Long COVID completed an online survey with over 400 questions. Nearly 90% of the ME/CFS group and just under 80% of the Long COVID group reported Post-Exertional Malaise. Over 80% had a formal diagnosis.
Top symptoms in both groups almost identical
Number 1: Fatigue. Number 2: Post-Exertional Malaise. Number 3: Brain Fog. ME/CFS and Long COVID showed a very similar symptom profile in this regard.
Highest positive resonance: Immunoglobulin and Antiretrovirals
These two treatment groups had the highest positive response rates – but also the smallest sample sizes. The results are promising, but require more data for confirmation.
Best overall score: Fluids, electrolytes and pacing
These approaches had the best overall score because they helped many people while at the same time having hardly any side effects. Important: Pacing is not a real treatment – it reduces symptoms through activity reduction, but is not a path to greater functional capacity.
Beta-blockers and ADHD stimulants: high efficacy, high risk
Many affected individuals reported improvements – but also significant side effects. With a low pulse, no beta blockers; with high blood pressure, no stimulants. Subgroup analysis shows: stimulants helped primarily the brain fog group.
Manual lymphatic drainage helped the most severely affected group the most
The severe multi-symptom group responded best to manual lymphatic drainage – an indication of the importance of the lymphatic system in ME/CFS.
Graded Exercise Therapy: the only treatment with a negative overall score
GET is the only treatment where the majority of respondents reported a worsening. It is the only one with a negative overall benefit score – a clear signal.
Subgroup analysis: four patient groups
Group 1: Severe multi-symptom group. Group 2: Orthostatic symptoms. Group 3: Brain fog-dominant. Group 4: Mildest severity. Different groups responded differently to the same treatments.
Key Learnings
- →Nearly 4,000 affected individuals: the largest treatment survey to date on ME/CFS and Long COVID
- →Fluids and electrolytes have the best overall score – effective and safe
- →Graded Exercise Therapy is the only treatment with a negative overall score
- →Pacing helps many people – but is not a real treatment, rather symptom management
- →Immunoglobulin and antiretrovirals promising – but small sample sizes
- →ME/CFS is heterogeneous – different subgroups need different approaches
- →All treatments should be discussed with a doctor before use – many have contraindications
Read full summary ↓
A peer-reviewed paper surveyed 3,925 ME/CFS and Long COVID patients about more than 150 treatments. The key findings: Immunoglobulin and antiretroviral medications had the highest positive response rates, but also the smallest sample sizes. Fluids, electrolytes and pacing had the best overall score – because they help many people and have hardly any side effects. Beta-blockers and ADHD stimulants helped many patients, but also harmed a significant minority. Graded Exercise Therapy is the only treatment with a negative overall score – the majority of respondents reported a worsening of their condition. The subgroup analysis reveals four patient groups that respond differently to treatments: a severe multi-symptom group, an orthostatic group, a brain fog group and a mild group. The author emphasises: This list is not a shopping list – all treatments have contraindications and should be discussed with a doctor. Statistically speaking: Even with a 25% chance of success per treatment, the overall probability increases significantly when multiple approaches are combined.
The Man Trying to Cure ME/CFS & Long Covid – Prof. Klaus Wirth on Mitodicure
Prof. Klaus Wirth & Carmen Scheibenbogen
Prof. Klaus Wirth explains his mechanistic overall model of ME/CFS – moving away from individual hypotheses toward a unified disease model. At the center is PEM as biological cell damage and MitoCure as the first targeted therapeutic approach.
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Paradigm shift: Comprehensive model instead of individual hypotheses
Wirth no longer asks: Is it viral? Autoimmune? Mitochondrial? Instead: What connects all the findings? A genuine disease model must simultaneously explain PEM, fatigue, pain, circulatory problems, POTS, and muscle damage.
Hypovolemia as the Core Mechanism
Less blood volume → less perfusion → less oxygen → more metabolic stress. Circulatory problems are not secondary – they are a central mechanism.
PEM is biological damage – not just exhaustion
Wirth's model: Overexertion → sodium overload → calcium overload → mitochondrial damage → muscle damage. PEM is a genuine cellular damage with measurable biological costs.
Dutch Muscle Biopsy Paper: Objective Evidence
Team around Rob Wüst showed: Before exertion, regeneration is visible; after exertion, damage and necrosis. PEM is thereby objectively proven as physical damage – not merely a worsening of symptoms.
Repeated PEMs accumulate damage
Every crash leaves biological costs. Crash avoidance is not comfort – but protection against progression and cumulative mitochondrial damage.
MitoCure: first targeted PEM mechanism approach
MitoCure is intended to stimulate the sodium pump, prevent calcium overload, and block mitochondrial damage. A completely different approach compared to symptomatic medications.
Healing through PEM interruption
If PEM maintains the illness and PEM is blocked, recovery can become possible again. Stop PEM → stop damage → enable regeneration.
Pacing remains mandatory even with medication
Even if MitoCure works: don't go full throttle straight away. Mitochondria need to regenerate first. The medication does not replace pacing – it expands the safe framework.
Key Learnings
- →ME/CFS could primarily be a disease of exertion-induced cell damage
- →PEM avoidance is the most important lever for stabilization or recovery
- →Perfusion and blood volume are central mechanisms – not a side issue
- →Every crash accumulates biological damage – relapse remains possible
- →MitoCure could be the first targeted approach to block the PEM mechanism
Read full summary ↓
Prof. Klaus Wirth and Carmen Scheibenbogen have developed a unified disease model for ME/CFS. The central idea: ME/CFS is primarily a disease of exertion-induced cellular damage. PEM is not a subjective symptom but genuine biological damage – demonstrated by muscle biopsies from the Dutch team led by Rob Wüst, which show regeneration before exertion and necrosis after exertion. The PEM mechanism: overexertion leads to sodium overload, then calcium overload, then mitochondrial damage. Beyond a certain intracellular sodium level, the transport mechanism tips over – this provides a biological explanation for the exertion threshold. MitoCure is intended to target precisely this point and interrupt the damage mechanism. Important: Even with medication, pacing remains mandatory, as mitochondria require time to regenerate.
Our ME/CFS Journeys: What Worked & What Didn't
Eleanor Stein & Patrick Ussher
Eleanor Stein and Patrick Ussher share honestly in this conversation what has helped with their ME/CFS illness and what has not. No cure protocol – but a realistic account of experiences with important misconceptions that many affected people make.
What helped
- ✓Florinef + Elektrolyte (mehr Blutvolumen, weniger orthostatische Intoleranz)
- ✓Sauna (Hormesis – kontrollierter Stress als Reiz)
- ✓AIP-Diät (massiver Wendepunkt nach 1,5 Jahren)
- ✓Molekularer Wasserstoff (Energie, Schmerz, Schlaf)
- ✓HELP-Apherese (ca. 20% Verbesserung bei Patrick)
- ✓Oral Rehydration Solution (schnelle Wirkung bei PEM)
- ✓Buteyko-Atemmethode (Schlaf, Nervensystemregulation)
What did not help
- ✗De Meirleir-Protokoll (keine Veränderung)
- ✗Cheney-Protokoll (keine Verbesserung, Hautprobleme als Nebenwirkung)
- ✗Shoemaker-Protokoll / CIRS (teuer, kein Nutzen)
- ✗Mitochondrien-Protokolle nach Sarah Myhill (kein Effekt)
- ✗Lange Antibiotikatherapie (kein Effekt)
- ✗LDN – Low Dose Naltrexone (2 Versuche à 6 Monate, keine Wirkung)
- ✗Hyperbare Sauerstofftherapie (Verschlechterung bei Patrick)
- ✗T3-Monotherapie (Cortisolabfall, Nebennierenprobleme)
Key Learnings
- →Pacing is not a supplement – it is the foundation of therapy
- →More treatment does not mean more healing
- →Therapies can actively cause harm – do not trust blindly
- →ME/CFS is highly individual – no standard solution
- →The body is not broken – it is trying to heal
- →Crash avoidance could be the central lever
- →Mitochondrial dysfunction could be a consequence, not a cause
Read full summary ↓
The conversation between Eleanor Stein and Patrick Ussher is not a healing protocol, but an honest account of years living with ME/CFS. Both describe a typical pattern: hope for a new therapy, a plausible theory behind it, high costs, a great deal of energy expenditure – often without effect. Eleanor Stein emphasizes: just because a theory sounds logical does not mean it holds true biologically for you. Both view pacing as an absolute foundation – not optional, but the basis of any therapy. Patrick raises a powerful thought: what happens if you don't crash at all for 100 days? He points to examples of significant recovery achieved through consistent crash avoidance. The three strongest levers from the conversation: pacing and crash avoidance, circulatory and blood volume management, as well as nutrition and systemic inflammation reduction.