2023/24 – Our Charity Year in Review – Investing

Investing in Biomedical Research into the causes, consequences and treatment of ME/CFS

Through the provision of funds, we aim to:

• Be an accessible source of finance for scientifically sound research from researchers (normally) at the beginning of their careers.
• Fund projects, the results of which produce findings to enrich the research world’s understanding of ME/CFS.
• Generate data for larger studies or to build upon for applications to central funding bodies; e.g. United Kingdom Research and Innovation/Medical Research Council.
• Encourage new researchers into ME/CFS research.

During the charity year to 31^st October 2024 the charity has invested a further of £349,693.50 covering 3 ME/CFS research projects in 3 countries.

There were no PhD-level research applications received in the year, but in August 2023 ME Research UK in conjunction with the Daphne Jackson Trust launched a Fellowship scheme, the aim being to further deepen the pool of ME researchers and research in the UK by enabling postdoctoral researchers to return to their profession after a hiatus through health or other issues. It is hoped that an announcement can be made early in 2025 over the charity’s first Fellowship.

In order to encourage and develop the next generation of researchers ME Research UK launched a Founders’ Science Writing Award on the topic of ‘The future of ME/CFS Research’. The international 1,000-word competition gives early career researchers the opportunity to develop skills in communicating science in a way that is accessible and engaging to the general public. The award honours the foresight of ME Research UK founders, Dr Vance Spence, Robert McRae and Roger Jefcoate CBE DL, in establishing ME Research UK as a major force in ME/CFS research globally. It also provides ‘real world’ experience in writing complex concepts in a language accessible to the public – a key and ever more important skill for researchers. A winner and runner-up have been selected with publication of their prize-winning entries scheduled for early 2025 in Breakthrough and online, as appropriate.

In summary, ME Research UK has 16 ongoing studies, including 3 newly funded projects and 4 PhD-level research projects, and these represent approximately £1.8 million currently invested in ME/CFS research globally. The research for which we have recently awarded funding covers a number of areas of interest, including electrophysiology, the brain and nervous system, and microvascular pathophysiology. The total value of awards given since 2000 now stands in excess of £4.5m.

New Research Projects in 2023/24

• Project 66 (offered prior to 31st Oct 2023 and accepted post 1st November 2023).
  Prof. Fatima Labeed, University of Surrey, UK, “The Electrophysiology of ME/CFS: Development of an Electrical Model for Exploration and Diagnosis.” (joint grant with the ME Association).
• Project 67
  Prof. Leighton Barnden, Griffith University, Australia, “Tracking changes in the structure and function of the brain over time in ME/CFS.”
• Project 68
  Rob Wüst, Vrije University Amsterdam, the Netherlands. “Skeletal muscle microclots and microvascular pathophysiology in ME/CFS.”

 Ongoing Projects in 2023/24

• Project 47
  Jarred Younger, University of Alabama at Birmingham, USA “Tracking peripheral immune cell infiltration of the brain in ME.”
• Project 55
  James Allison, Newcastle University, UK, “EluCidATe: Exploring pain and autonomic dysfunction in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Temporomandibular disorders.”
• Project 59
  Amy Proal, PolyBio Research Foundation, Medford, MA, USA, ” Use of advanced metagenomic technologies for the identification of viruses in ICC-diagnosed ME/CFS patient tissue and nerve biopsy samples.”
• Project 60
  Prof Simon Carding, Quadram Institute, Norwich, UK, “Gut eukaryotic viruses as a player in ME/CFS.”
• Project 61
  Dr Eliana Lacerda & Prof. Geraldine Cambridge, London School of Hygiene and Tropical Medicine & UCL, UK, “Antibody Discovery using Novel Microarray of Functional Proteins in patients with Myalgic Encephalomyelitis/Chronic Fatigue syndrome: a pilot study.”
• Project 62
  Dr Zack Shan, University of the Sunshine Coast, Australia. “Non-invasive MR imaging of chronic neuroinflammation in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).”
• Project 63
  Dr Bo Christer Bertilson, Medect Clinical Trials, Bragée Clinics, Sweden. “Proteomic and metabolomic analyses to reveal biomarkers of ME/CFS – a case-control study of blood and spinal fluid.”
• Project 64
  Prof. Janet Taylor, Edith Cowan University, Australia. “Investigation of motoneurone firing behaviour and associations with symptom severity in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.”
• Project 65
  Prof. François-Jérôme Authier, Henri Mondor University Hospital, France. “Neurocognitive impairment in Myalgic Encephalomyelitis (ME): Neuropsychological evaluation and functional brain imaging study – COGNIME 2022.”

PhD-level research projects

• PHD – 002
  Prof Chris Ponting, University of Edinburgh, UK. “Experimental investigation of genetic risk factors for ME/CFS revealed by the DecodeME project.”
• PHD – 003
  Dr Sarah Annesley, La Trobe University, Australia. “Cause-effect relationships in the mitochondrial energy inefficiency in ME/CFS.”
• PHD – 004
  Prof. Jo Nijs, Vrije Universiteit Brussel, Belgium. “Mitochondrial dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): are autonomic phenotypes necessary to clear conflicting results?”
• PHD – 005
  Dr Douglas Barrett, Leicester University, UK. “Impaired selective attention as a cognitive and neurophysiological markers of ME/CFS.”

 Projects Completed in 2023/24

• Project 54
  Elisa Oltra, Catholic University of Valencia, Valencia, Spain. “Metabolic impact of activated HERVs and associated innate immune response in severe ME: towards disease modelling.”
• Project 56
  Prof Bhupesh Prusty, Julius-Maximilians-Universität Würzburg, Germany. “Understanding potential infectious triggers behind mitochondrial dysfunction in ME/CFS.” The results of this study are yet to be published.
• Project 57
  Prof Leighton Barnden, Griffith University, Australia. “Increased brain neurochemical levels in ME/CFS and long COVID.”
• Project 58
  Sarah Annesley, La Trobe University, Australia. “Cell type specificity, molecular scope and epigenetic basis for mitochondrial and cellular dysfunction in ME/CFS cells.”

 Projects not being completed

PHD-001 – Alfredo Iacoangeli, King’s College London, UK (Identification of new classes of genetic susceptibility to ME). Due to changes in circumstances the research contracted could not be completed and the grant (funded jointly with Action for ME) was brought to an end. Non-utilised funds revert to being available to invest in new projects.

Impact and Scientific Publications

A widely accepted means by which the work of the charity can be assessed is to gauge the number of scientific publications emanating from specific projects. Four papers were published by researchers in the charity year 2023/24 acknowledging the support of ME Research UK.

• Inderyas M, Thapaliya K, Marshall-Gradisnik S, Barth M, Barnden L. Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Neuroscience, 2024.
• Annesley SJ, Missailidis D, Heng B, Josev EK, Armstrong CW. Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies. Trends in Molecular Medicine, 2024; 30(5):443–58.
• Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, Eftekhari Z, Inderyas M, Barnden L. Imbalanced brain neurochemicals in long COVID and ME/CFS: a preliminary study using MRI. The American
  Journal of Medicine, 2024; Epub.
• Giménez-Orenga K, Martín-Martínez E, Oltra E. Over-representation of torque teno mini virus 9 in a subgroup of patients with myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. Pathogens, 2024; 13(9):751.

Key Findings of ME Research UK researchers within the year

• ME/CFS and long COVID patients had larger than normal volumes of several areas of the brainstem, and these volume changes correlated with clinical measures of pain and breathing difficulty. (Project 57)
• In people with ME/CFS and those with long COVID, functional connectivity (i.e. communication) was impaired between areas of the brain involved in movement, cognitive function, sensory processing, the sleep–wakefulness cycle, self-awareness and autonomic responses. In addition, functional connectivity was associated with respiration, length of illness, fatigue severity, pain intensity and memory scores. (Project 57)
• Levels of glutamate (a neurotransmitter) in the brain were increased in ME/CFS and long COVID patients, while levels of N-acetyl-aspartate (which has a number of functions) were increased in long COVID. In both patient groups, neurochemical levels correlated with the severity of symptoms such as physical function, cognitive impairment, unrefreshing sleep and pain. (Project 57)
• Increased levels of a virus called TTMV9 were detected in people with ME/CFS and activated HERVs, suggesting that this virus has potential as a biomarker for the disease in this subgroup of patients. While TTMV9 is normally found in humans, high levels could indicate abnormal immunity, and the researchers found associations between TTMV9 and altered HERV and immunological profiles in these patients. (Project 54)

It is also telling the number of ME Research UK-funded researchers who are asked to speak on research topics. Such invitations cement ME Research UK’s reputation and demonstrate the charity’s ability to fund the highest quality researchers.

• April 2024’s 1st International Conference on Clinical and Scientific Advances in ME/CFS and long COVID
  Dr Luis Nacul (Treatment of ME/CFS: Beyond the NICE Guidelines on Diagnosis, and Recommendations), Dr Eliana Lacerda (A Prospective Cohort from the UK ME/CFS Biobank (UKMEB): Participants with Mild/Moderate or Severe ME/CFS), Dr Nuno Sepúlveda (3 presentations Reflections and Implications for Clinical Practice and Policies in Portugal, Research Challenges in ME/CFS and Long COVID in the Era of Machine Learning and Artificial Intelligence, and Reflections and Implications for Research and Scientific Collaborations in Portugal), and Prof. Carmen Scheibenbogen (Autoimmunity in ME/CFS and Post COVID Syndrome and Treatment Trials).  In addition, Drs Nacul and Lacerda also moderated a Panel Discussion.
• May 2024’s International Conference on Long Covid and ME/CFS (remotely) UniteToFight2024
  Prof. Carmen Scheibenbogen (ME/CFS as part of the post-COVID spectrum), Dr. Rob Wüst (Skeletal muscle function and post-exertional malaise in patients with Long-COVID), Dr Amy Proal (Pathogen persistence in Long Covid and ME/CFS: evidence and research considerations), and Prof Bhupesh Prusty (Overlapping and differentiating biological features of ME/CFS and Long Covid).
• June 2024’s 16th Invest in ME Research International ME Conference  held near Cambridge, UK. Prof Simon Carding (Updates on research into ME, ), Dr Rob Wüst (Explaining skeletal muscle-related symptoms in patients with ME/CFS: from skeletal muscle to exercise immunology).
  During the 13th Biomedical Research into ME Research Colloquium which preceded the Conference, ME Research UK researchers Professors Simon Carding and Lenny Jason, and Dr Elisa Oltra either chaired meetings or presented. ME Research UK also provided travel costs for PhD-level researcher (PHD-03) Tina Katsaros to attend.

Introduction | Informing | Influencing