Overview
ME Research UK attended “The 16th Invest in ME Research International ME Conference 2024”, which was held at the Wellcome Genome Campus in Hinxton, Cambridgeshire, on 28th June 2024. The conference featured a variety of presentations and discussions centred on advancing research and clinical trials in ME/CFS. Videos of the presentation are available via Youtube.
Key Highlights
Push for Clinical Trials
Dr Vicky Whittemore outlined the development of the NIH ME/CFS Research Roadmap, highlighting the contributions of eight working groups focussed on different areas: chronic infection, immune system, nervous system, circulation, metabolism, physiology, less-studied pathologies (e.g. mast cell activation syndrome; MCAS), and genetics. Key questions addressed included: “What do we know?”, “What don’t we know?”, and “What do we need to know to move towards clinical trials?”.
Dr Whittemore emphasised the importance of:
- Rigorous research which captures, and addresses differences between people with ME/CFS (heterogeneity).
- Collaboration between researchers, clinicians, people with lived experience of ME/CFS and advocacy groups.
- Engagement with stakeholders (e.g. federal agencies, non-profit organisations, people with lived experience, and pharmaceutical/biotech companies).
- Utilising existing clinical trial networks and drug repurposing.
- Moving research beyond looking at “just blood” – a priority also mentioned by Dr Amy Proal in her talk at the Unite to Fight conference.
Regrettably, she also mentioned that the NIH budget has been cut this year and is going to be significantly worse next year
Effort Preference – Not a Big Deal?
Dr Brian Walitt presented results from the NIH’s intramural deep phenotyping study of ME/CFS. He highlighted the significance of birth sex in understanding post-infectious ME/CFS, but notably did not discuss “effort preference”, a central and controversial theme of the published paper. When later asked about this by an ME Research UK representative, he stated that “decision-making” only plays a small role in ME/CFS mechanisms. He directed attendees to a 5.5-hour seminar for comprehensive insights. ME Research UK has provided both a basic and detailed overview of the paper.
Muscle Damage/Changes Beyond Deconditioning
Dr Rob Wüst presented his findings on muscle changes in individuals with long COVID, and emphasised how counterproductive exercise can be for individuals with long COVID, and for those with ME/CFS, especially beyond the “post-exertional malaise (PEM) threshold”. His research revealed that there were fewer red muscle fibres in people with long COVID, and that amyloid-containing deposits/“clots” increased post-exercise. Additionally, the team conducted a study where 60 healthy individuals underwent 60 days of bedrest in order to induce deconditioning. The findings suggest that the muscle changes seen in healthy participants with induced deconditioning are not the same as those observed in studies looking at people with ME/CFS – indicating that deconditioning alone does not explain ME/CFS symptoms.
During the Q&A, an audience member commended his research as “one of the most significant contributions in the past 12 months.” Funded by ME Research UK, Dr Wüst and colleagues are extending their research to individuals with ME/CFS.
Selenium and Iodine Deficiency
Professor Lutz Schomburg discussed the potential link between selenium (Se) and iodine deficiency and autoimmunity in ME/CFS, highlighting the role of selenoprotein P (SELENOP).
SELENOP is a selenium containing protein in the liquid part of blood (plasma) that plays a pivotal role in selenium metabolism – a decrease in SELENOP causes various dysfunctions related to Se deficiency – of which the symptoms include muscle weakness, fatigue, mental fog, and a weakened immune system, and increased oxidative stress – which has also been observed in people with ME/CFS.
Professor Schomberg noted that iodine and selenium are both essential for healthy function of the thyroid gland, and for production of thyroid hormones. Thyroid hormones, such as “T3” are responsible for activating the energy production process the mitochondria.
One study mentioned found a “Higher prevalence of Low T3 syndrome” in people with “Chronic fatigue syndrome” (CFS). Effects of “low T3 syndrome” include increased levels of inflammation and a reduction in metabolism to save energy. It is worth noting two key limitations of this study:
- The study was cross sectional meaning that it is impossible to establish direction of effect from the findings i.e., does “CFS” lead to low levels of T3, or is it the low T3 which is leading to “CFS”?
- Participants in the study were diagnosed with “CFS” using guidelines based on the Fukuda criteria, which do not require the presence of PEM for a diagnosis to be made.
Immune Exhaustion in ME/CFS
Dr Maureen Hanson expanded on a topic that has been generating increasing attention in ME/CFS research – immune exhaustion – a state where immune cells, particularly T-cells, lose their ability to effectively respond to foreign antigens/infections. Genetic analysis showed that exhaustion markers were elevated in ME/CFS T-cells compared to controls. Dr Hanson also noted that higher fatigue scores correlated with increased diseased monocytes (another type of immune cell).
Insights from Long COVID
Professor Nancy Klimas discussed insights from long COVID research, asking the question – what have we learned about long COVID that might help individuals with ME/CFS? One paper highlighted during the talk suggested that “brain fog,” i.e. cognitive impairment, in long COVID is associated with blood-brain-barrier (BBB) disruption and systemic inflammation.
Clinical Management Approaches
Clinicians – Dr Irina Rozenfield, Dr Violetta Renesca, and Dr Jesper Mehlsen – discussed their approach to patients with ME/CFS and whether there are differences in management in the USA vs Europe. In the USA, a personalised approach – which recognises that ME/CFS differs between people with the disease, is used. It was also noted that a shortage of any nutrient can lead cells to malfunction, therefore disease management plans included nutrition alongside lifestyle changes, stress management, and working to improve sleep – especially increased deep sleep, and immune function.
In Europe, a personalised approach was also mentioned, for example when considering use of low dose naltrexone in people with ME/CFS “you need to find the right dose for the patient”. At least in Nordic countries, there are not enough doctors who are able to treat and diagnose ME/CFS, but Dr Mehlsen is developing a tool which he hopes can be used in daily clinical practice to help diagnose and treat ME/CFS.
Also highlighted was the necessity of recognising that activities of daily living (ADLs) can be considered as exercise for many with ME/CFS, and the importance of managing comorbidities such as dysautonomia.
AI in ME/CFS Research
Dr Dezsö Modos discussed the use of artificial intelligence and the mapping of biological networks to uncover hidden pathways in complex diseases, such as inflammatory bowel disease, and the potential for these techniques to be applied to better understand ME/CFS.
Clinical Trials for Pyridostigmine and Low Dose Naltrexone (LDN)
Dr David Systrom recapped much of what was presented at the “1st International Conference on Clinical and Scientific Advances in ME/CFS and Long COVID” which took place in Lisbon earlier this year. In addition, he discussed drug repurposing clinical trials related to pyridostigmine (Mestinon) – a drug usually used to improve muscle weakness in people with myasthenia gravis, and low dose naltrexone (LDN) – naltrexone is a drug which targets specific receptors in the brain and can reduce pro-inflammatory agents. There is evidence that points to “remarkable improvement” of oxygen uptake in participants with ME/CFS who took pyridostigmine, and that LDN may restore natural killer cell (immune cell) function and downregulate inflammation. Dr Systrom discussed the proposed LIFT study – a clinical trial involving pyridostigmine, LDN, and placebo – and exclusively including individuals with a diagnosis of ME/CFS pre-COVID pandemic.
BH4 Hypothesis
Professor Ron Davis introduced the hypothesis that a molecule known as BH4 could be involved in the pathogenesis of ME/CFS. BH4 is important in metabolic reactions within the body but is difficult to study because of its particularly small size and the fact that it is lost rapidly from blood samples. Nevertheless, Professor Davis has begun recruiting participants to look at BH4 – this is probably the first time this has been done.
Conclusion
The 16th Invest in ME Research Conference provided significant insights and updates on ME/CFS research, highlighting the importance of collaboration, innovative research methods, and clinical trials to improve understanding and treatment of this complex condition.
