Agents for Change IIMEC10

IIMEC10 London, May 2015

Our 10th Invest in ME International ME Conference 2015 - IIMEC10 - took place on 29th May 2015 in London and attracted delegates from seventeen different countries - from Europe, North America, Middle East and Australasia.

The theme for IIMEC10 was Agents for Change - reflecting the gathering inititaives, individuals and organisations that are playing key roles in developing research into ME and changing the perception of this disease. Through the multiple international collaborations the charity has formed there is a real sense of progress being made in understanding this disease and applying meaningful science with a firm strategy of biomedical research.

Prior to the IIMEC10 conference the charity held a two-day Biomedical Research into ME Colloquium - our fifth annual colloquium. Together these three days brought together a large group of researchers (both new to ME and experienced ME researchers) to collaborate and share knowledge about research for the benefit of future research. With our conference and two day research colloquium on the days before the conference we brought together different aspects of researching this disease in the hope that combining ideas and experiences of biomedical research into ME and collaborating in future research would enhance education and effectiveness of research efforts.

Research into Myalgic Encephalomyelitis - specifically biomedical research into ME - has become a mainstream area of research and the charity is now working with major academic and research institutions in several countries. ME research now attracts interest from a wide range of specialities. Those clinicians and researcher who have worked very hard over the years to get this disease taken seriously are witnessing a change in attitudes. Now this needs to be reflected in research funding allocation. It is only a matter of time when patients can see real progress in many areas of their lives.

The IIMEC10 conference brought to London some of the major initiatives being taken in ME research. The events organised by Invest in ME are based on a collaborative strategy of biomedical research into ME which we believe will progress this complex but exciting area of research and eventually lead to appropriate development of patient care and treatments for people with ME. The mainstreaming this field of research has been one of the major achievements of the IIMEC* conferences.

Past IiME Conferences

The conference regularly attracts clinicians, researchers, healthcare staff, charities, support groups and patients and carers fromtwenty countries around the world.
This allows unique networking opportunities and increase the potential for one of the charity's main objectives - international collaboration between researchers.

IIMEC10 Conference Agenda 2015

Lecture Theatre Birdcage Walk

Conference Speakers

Former Dean of Biological Sciences, UEA

Dr Ian Gibson, former Labour MP for Norwich North, worked at University of East Anglia for 32 years, became Dean of the school of biological sciences in 1991 and was head of a cancer research team and set up the Francesca Gunn Leukaemia Laboratory at UEA. In 2011 Dr Gibson received an honorary doctorate of civil law from UEA.

Director Institute of Food Research, Norwich, UK

Professor Ian Charles joins the Institute of Food Research in May 2015 to lea d the programme to develop the UK’s new Centre for Food & Health to be ba sed at the Norwich Research Park. Professor Charles is returning to the UK from Australia where he was Director of the ithree institute, University of Technology, Sydney. Professor Charles has over 30 years’ experience in academic and commercial research. His academic career has included being a founding member of The Wolfson Institute for Biomedical Research at University College London, one the UK’s first institutes of translational medicine. He has also worked in the pharmaceutical industry at Glaxo Wellcome, and has been founder and CSO of biotech companies in the area of infectious disease, including Arrow Therapeutics, sold to AstraZeneca, and Auspherix a venture capital backed company founded in 2013. His current research interests include infectious diseases as well as the microbiome and its impact on health and wellbeing. The new Centre for Food & Health will provide a step change for food and health research, and the translation of science by industry, to benefit society and the UK economy. The Centre will be located at the Norwich Research Park, one of Europe’s largest single-site concentrations of research in Food, Health and Environmental sciences. The multidisciplinary Centre aims to bring together the Institute of Food Research and aspects of the University of East Anglia’s Faculty of Science and the Norwich Medical School with the regional gastrointestinal endoscopy facility at the Norfolk and Norwich University Hospital. With a unique integration of diet, health, nutrition and medicine under one roof, linking closely to world class plant and crop research at the John Innes Centre and bioinformatics at The Genome Analysis Centre (both also located on the Norwich Research Park), it will have the potential to deliver clinically validated strategies to improve human health and wellbeing.

Center for Infection and Immunity (CII), Columbia University Mailman School of Public Health New York, USA

Mady Hornig, MA, MD is a physician-scientist in the Center for Infection and Immunity (CII) at the Columbia University Mailman School of Public Health where she serves as Director of Translational Research and is an associate professor of epidemiology. Her research focuses on the role of microbial, immune, and toxic stimuli in the development of neuropsychiatric conditions, including autism, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection), mood disorders and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). She is widely known both for establishing animal models that identify how genes and maturational factors interact with environmental agents to lead to brain disorders and for her work clarifying the role of viruses, intestinal microflora and xenobiotics in autism and other neuropsychiatric illnesses that may be mediated by immune mechanisms. Under her direction, proteomic analyses of umbilical cord samples are identifying potential birth biomarkers for autism in a prospective study in Norway, the Autism Birth Cohort (ABC). She established that there was no association between intestinal measles virus transcripts and autism, and, with Brent Williams and W. Ian Lipkin at CII, has found altered expression of genes relating to carbohydrate metabolism and inflammatory pathways and differences in the bacteria harboured in the intestines of children with autism. She also leads projects examining the influence of immune molecules on brain development and function and their role in the genesis of schizophrenia, major depression, and cardiovascular disease comorbidity in adults, and directs the Chronic Fatigue initiative Pathogen Discovery and Pathogenesis Project at CII. In 2004, Dr. Hornig presented to the Institute of Medicine Immunization Safety Review Committee and testified twice before congressional subcommittees regarding the role of infections and toxins in autism pathogenesis. Her work in ME/CFS is establishing immune profiles and helping to identify pathogens that may be linked to disease.

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Full Chair Professor in Analytical Chemistry and Neurochemistry at the Department of Chemistry, Uppsala University, Sweden

Professor Begquist has a background as MD, Associate Professor of Clinical Neuroscience , Sahlgrenska University Hospital and the University of Gothenburg. Since 1999 , he has been a researcher in Uppsala, Sweden, and in 2005 was appointed professor of analytical chemistry and neurochemistry at the Department of Chemistry - BMC , Uppsala University. From 2011 he worked also as an adjunct professor of pathology at the University of Utah, Salt Lake City, Utah, USA. Professor Begquist was elected as Fellow of the Royal Chemical Society in 2015.

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Epsom and St Helier University Hospitals NHS Trust,Surrey, UK

Consultant Clinical Immunology and Immunopathology Epsom and St Helier University Hospitals NHS Trust Surrey, UK Dr. Bansal trained in immunology and allergy from 1989 to 1993 at St. Mary's Hospital in Manchester and at Hope Hospital in Salford. From here he spent five years (1993-1997) as Senior Lecturer and Consultant in Clinical Immunology in the Department of Medicine at the Princess Alexandra Hospital in Brisbane, Australia. From 1997 to the present date Dr. Bansal has worked as a Consultant in Clinical Immunology and Immunopathology at Epsom and St Helier University Hospital. Dr Bansal's key interests lie in allergy, autoimmunity, ME/CFS and immunodeficiency. Dr Bansal is involved in the gut microbiota study at UEA, the IiME/UCL rituximab clinical trial and Autoimmunity and ME, a study involving the hypothalamus - all projects funded by Invest in ME. Research from Dr Bansal

Further Information

London School of Hygiene and Tropical Medicine, UK

Dr Luis Nacul is Honorary Clinical Senior Lecturer at London School of Hygiene and Tropical Medicine

Griffiths University, Australia

Professor Marshall-Gradisnik is one of Australia's foremost researchers in the area of neuroimmunology and has been instrumental in establishing the Public Health and Neuroimmunology Unit (PHANU) at Bond University. Much of her work relates specifically to autoimmunity in Chronic Fatigue Syndrome sufferers and she is regularly asked to speak to community groups on behalf of Queensland Health and NSW Health. Her research in the area of exercise immunology has also contributed to the body of knowledge relating to the effect of doping in sport and she serves as Sports Medicine Australia's national spokesperson in this area. The vital research conducted by Professor Marshall has attracted more than $1 million in grant funding and she has produced 21 peer-reviewed papers, five book chapters and one provisional patent. In 2008 Dr Marshall was joint leader of the Bond University team responsible for developing the the BioSMART program. The team was awarded a prestigious Australian Teaching and Learning Council Award (formerly known as the Carrick Award) for Outstanding Contribution to Student Learning and for the quality of student learning over a sustained period of time. Professor Marshall-Gradisnik is also leading The National Centre for Neuroimmunology and Emerging Diseases (NCNED), a research team situated at Griffith University on the Gold Coast. The team focuses on Myalgic Encephalomyelitis.

Further Information

Leader, Gut Health and Food Safety Programme Institute of Food Research, Norwich Research Park, UK

Professor Simon Carding Professor of Mucosal Immunology at University of East Anglia and Institute of Food Research. Following his PhD at London he held postdoctoral positions at New York University School of Medicine, New York and at Yale University School of Medicine, New Haven, USA. He then moved to the University of Pennsylvania, Philadelphia, USA as Assistant and later Associate Professor. He joined University of Leeds as Professor of Molecular Immunology in the Institute of Molecular and Cellular Biology in 1999. His scientific interests are in understanding how the immune response in the gut functions and in particular, is able to distinguish between the commensal microbes that reside in the gut and environmental microbes that cause disease, and in the mechanisms by which the body's immune system no longer ignores or tolerates commensal gut bacteria and how this leads to immune system activation and inflammatory bowel disease.

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PhDs and Students Funded by Invest in ME (Research)

From left to right:

Bharat Harbham is a fourth year medical student at University of East Anglia

Fane Mensah is a PhD student at UCL, London, UK

Dr Ian Gibson (Chair)

Professor Siimon Carding (session chair)

Navena Navaneerathaya is a fourth year medical student at University of East Anglia.

Daniel Vipond is a PhD student at UEA/IFR, Norwich, UK

Further Information

Principal Research Fellow Inflammation, Div of Medicine Faculty of Medical Sciences, UCL

Dr Cambidge's group focuses its interests on B cell depletion (an idea which they introduced (with the Professor Jo Edwards) approximately 10 years ago for the treatment of rheumatoid arthritis), exploring more precisely how the technique works and trying to explain the marked variation in response between different patients.

Further Information

Honorary Consultant Neuropsychiatrist, Brighton & Sussex Medical School, UK

Dr Harrison's' work in the laboratory focuses on understanding how infection or inflammation in the body interacts with the brain. For most these symptoms are usually short lived and relatively mild. However, when the immune system is activated for long periods, such as in people suffering from rheumatoid arthritis, they can become extremely debilitating or even life-threatening. Understanding how the immune system interacts with the brain is a crucial first step that will form the foundations for future development of novel therapies targeting these common and disabling symptoms. Most of his studies utilise a combination of functional brain imaging (e.g. fMRI, FDG-PET, EEG, polysomnography), experimental models of inflammation, custom cognitive tasks and diverse measures of peripheral immune status.

Further Information

Infectious Disease Specialist, Torrance, California, USA

Dr Chia is an infectious disease specialist practicing in Torrance, California, USA and has published research recently (Chronic fatigue syndrome associated with chronic enterovirus infection of the stomach) on the role of enteroviruses in the aetiolgy of ME/CFS – an area which has been implicated as one of the triggers by a number of studies. There are more than 70 different types of enteroviruses that can affect the central nervous system, heart and muscles, all of which is consistent with the symptoms of ME/CFS. By analyzing samples of stomach tissue from 165 patients with CFS, Dr. Chia's team discovered that 82% of these individuals had high levels of enteroviruses in their digestive systems. Dr Chia's research may result in the development of antiviral drugs to treat the debilitating symptoms of ME/CFS. Dr Chia is President of the Enterovirus Foundation and Assistant Professor at the UCLA School of Medicine.

Further Information

University of Leicester, UK

Lecturer in the College of Medicine, Biological Sciences and Psychology at the University of Leicester
Claire Hutchinson is a vision scientist. The majority of her work is concerned with how visual sensory information is encoded by the human visual system. Her research includes healthy visual perception, age-related visual decline, and visual markers of 'non-visual' illnesses. It is this latter strand of research that led her to study vision-related problems in ME/CFS.

Further nformation

Ithaca College, USA

Professor Keller is Professor Ithaca College, Dept. of Exercise and Sport Sciences, Ithaca, NY. RESEARCH / CLINICAL FOCUS: Since 2003 Professor Keller has tested persons ill with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) for purposes of research and/or to provide an objective assessment of functional capacity and ability to perform and recover from physical work. Often, these individuals seek an objective indication of illness status to apply for disability benefits. A two-day exercise test protocol has shown to be instrumental in delineating abnormal responses to and recovery from exercise in ME/CFS patients. Her report of test results and interpretation has been successful in many cases to support an argument for disability coverage. There are only a few researchers in the USA who have performed and interpreted the two-day exercise test protocol on ME/CFS patients, and therefore have observed first-hand the anomalous multisystem responses of these patients 24 hours post-exercise. Professor Keller continues to expand the small body of peer-reviewed evidence of the abnormal recovery response to physical activity in ME/CFS so that most, if not all clinicians, researchers, health insurers and patient family members also understand the deleterious impact of this illness. To that end, She has collaborated on an NIH R21 grant with PI, Maureen Hanson, from Cornell University to study the effects of exercise in ME/CFS on parameters of physiological and immune function. Together they continue to analyze this data and other data collected to better understand how to help those with ME/CFS.

Further nformation

Haukeland University Hospital in Bergen, Norway

Professor Mella has performed clinical trials to test the benefit of B-cell depletion therapy using Rituximab in ME/CFS patients. Dr. Olav Mella of Haukeland University Hospital in Bergen, Norway began his investigation of Rituximab’s effects on CFS after treating several Hodgkin’s Lymphoma patients who had long standing cases of CFS prior to developing cancer. Professor Mella and Dr Fluge have published a paper "Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study"

Further nformation


Conference Report



by Dr Rosamund Vallings MB BS

Conference ReportIIMEC10 Conference Report

10th Invest in ME International ME Conference

29th May 2015, London

I was privileged to attend the 10th Invest in ME conference in London on 29th May 2015 following on from the 2-day colloquium attended by 60 invited delegates from around the world. Participants from 17 countries were welcomed to the conference opening by Invest in ME and the chair was then taken by Dr Ian Gibson .

The keynote speech was given by Professor Ian Charles (Norwich, UK). He has recently been appointed by the Institute of Food Research to lead the programme to develop the UK’s new centre for Food and Health based at Norwich Research Park.

This is a large complex incorporating: The Institute of Food Research, The University of East Anglia, the Norfolk and Norwich University Hospital and the Genome Analysis Centre. There will be interdisciplinary approaches to address many complex problems.
He discussed the gut microbiome, explaining that we have ten times more bacteria than cells.

He asked the questions: “Do alterations in intestinal barrier integrity and microbiota exist in ME?” and “Is there evidence of immune exposure and reactivity to commensal microbes in ME patients?” He will be working within an interdisciplinary model, which will become an international hub for food and health research, with top class scientists appointed. Many departments will be working together.

This new approach will be holistic, systematic and integrated to deliver faster innovation. It will be a site of excellence and will liaise with government. The aim is to lead to personalized nutrition to benefit the individual microbiome.

The first presentation was given by Mady Hornig (Columbia, USA). She discussed markers of immunity and metabolism in ME. She described a 3-strikes hypothesis regarding development of the illness, involving genes, environment and timing.
These affect brain outcomes, and she discussed the effects of the mother’s own immune system on the developing foetal brain. Her cytokine profile could be implicated in the risks of the infant developing nervous system disorders, even years later.
The microbiome of the mother also influences the offspring’s immune system with potential risks. Many disorders of the nervous system may stem from immune-mediated pathogenesis. She then described how there is an increase in plasma levels of pro-inflammatory cytokines associated with recent illness in ME, and as the illness progresses, these levels fall. A striking finding is the very high level of IFN-gamma in short duration illness.
It is possible that different cytokine profiles may affect the potential benefit of different types of therapies. Therapies may need to be different at different stages of the illness. Looking at the cerebrospinal fluid (CSF) comparing ME, MS and controls, there were some similarities between ME and MS but the controls had very different immune signatures. The patterns of immune molecules in the CSF of ME subjects, who largely had been ill for many years, were similar to those observed in Hornig et al.’s immune profiling studies using blood from ME subjects of long-standing duration. Discussing metabolomics, she then described 7 classes of 180 metabolites.
Alterations were found in a wide range of metabolites in ME, including ADMA, which is associated with nitrosative stress, and in tryptophan and serotonin.
These metabolomic changes were found to be correlated with changes in cytokines.
In the gut, there may be imbalances due to foods leading to bacterial fermentation.
Probiotics and faecal transfers do have potential, as have been found to prevent encephalopathy in cirrhosis of the liver.
A question was asked as to whether the effects of SSRIs may be affected by the serotonin levels and whether the duration of the illness could be implicated here.
It may be that patients will need to be categorized according to illness duration, and there may be a subgroup who will respond. But serotonin levels are not the only mechanism.
It is likely to be more complex than that.

Jonas Berquist (Uppsala, Sweden) describing himself as an analytical chemist, discussed the Proteomics in ME/CFS. The first ever analytical chemist was Tobern Olaf Bergman from Sweden. So there is a strong Swedish tradition in this field. Berquist’s lab does general research and uses mass spectrometry looking at endogenous analytes. He described proteomics as life’s molecular machines – i.e. proteins which carry out all functions of the body.
He looked at when, where, how proteins are expressed. Post-translational modifications (PTMs) occur. This can be measured using 3D gel electrophoresis, but nowadays “shotgun” proteomics is used to separate them out. Many instruments are used and some of them are very big machines, using high resolution mass spectrometry. It is important to use the correct samples from serum and tissues. The tests are extremely sensitive. He compared the small concentrations measurable with these techniques as the amount found if a cup of coffee is poured into a swimming pool.

When looking at the CSF, the total volume is about 150ml and 5-600ml daily is produced. Sample handling needs to be extremely careful. His labs have produced a 776 page list of the peptides in the CSF. There are different ranges with overlaps in different conditions. The study gives meaningful insights into the biological processes in ME/CFS. There are significantly changed proteins involved in neurologic, metabolic and immune diseases. He has looked at upstream and downstream analysis.

The conclusion is that this work could lead to biomarkers, which maybe diagnostic, prognostic and therapeutic.

Luis Nacul (London, UK) reviewed the epidemiological evidence on ME/CFS looking at the current status and implications for research and service delivery. He described it as a jigsaw coming together. He felt that the symptoms of encephalitis were very similar to the symptoms of ME, which MAY therefore BE indicative of neuro-inflammation. He said that the diagnosis of ME SHOULD BE DISTINGUISHED FROM THAT OF Chronic Fatigue Syndrome, AS usually the term ME was indicative of more symptoms. He mentioned a variance in prevalence rates, with females more commonly affected than males. Overall population estimates are between 0.1% and 0.7%. Young adulthood is the commonest age of incidence. In patients with ME/CFS, activity is significantly diminished. He stressed that we need to look at specificity and sensitivity, and risk ratio and risk difference. Specificity should take precedence over sensitivity for validity.

The NICE guidelines on management were mentioned. There are limited effects shown in the clinical response to CBT. But the results may not be valid as studies used in the meta- analyses are of poor quality and a large proportion of patients did not complete a trial, and therefore results may not be valid. It could be described as an additional “coping” therapy, which should not distract us from finding specific treatments for ME.

We need to concentrate on biomarkers for the future, with case stratification and intervention strategies. The current UK biobank has 500 participants, with 17,000 aliquots stored as of March 2015.

Amolak Bansal (Surrey, UK) gave an overview of the diagnosis and differential diagnosis on ME. He explained how fatigue occurs in many illnesses, but is the cardinal feature of ME/CFS. He said the post-exertional malaise is hard to explain. He then went through the various criteria being used to diagnose the illness. He discussed the differences between the criteria (CDC, ICC etc.). He thinks that the term SEID may be too simple. He talked of exclusion criteria, including temporary exclusion criteria, such as hypothyroidism and morbid obesity leading to sleep apnoea; and psychiatric exclusion criteria. He mentioned comparisons which are made between the terms CFS and ME.

He then went through the Sutton scoring system developed at his clinic. The main symptoms have a “loaded” score: e.g. PEM scores 3 points, sleep problems 2 and all other symptoms 1 point. 8 or more points out of 13 points is needed for a diagnosis. All patients must have post exertional malaise. For subjects involved in research he uses a score of 10+ from 13 to ensure a critically well-defined population. Subjects with a significant depression or anxiety are excluded from research but can still be diagnosed with ME/CFS for management purposes if they have sufficient points and the depression and anxiety is secondary to the ME/CFS. Treating the depression, anxiety and ME/CFS are all critical to improvement in these people. It is important to note that sensitivity to medication, and alcohol intolerance are very common in ME/CFS. Fewer than 10% patients can tolerate alcohol. Another unusual sign in 60 % patients is altered pupillary reflexes (alternating dilatation and contraction while a light is shined) and sighing respirations. Other physical signs include: joint hypermobility (20%), increased respiratory rate (80%), coldness of peripheries (70%). Conditions that can cause symptoms similar to ME/CFS include: hypothyroidism, Addison’s disease, pituitary dysfunction, Sjogren’s syndrome, gluten sensitivity, persistent anxiety, primary sleep disorder, Ehlers Danlos Syndrome joint/hypermobility type, cardiac dysfunction, Parkinson’s disease and temporo-mandibular joint disorder.

He then compared ME/CFS with depression and anxiety. The sleep disturbance in ME/CFS is different to that in depression and the former are also markedly hypersensitive to psychoactive medications. Functionally those with ME/CFS can start a task, but then trend downwards while those with depression cannot start a task as they have reduced motivation, but once started they can often manage to complete it. Those with ME/CFS rarely resort to alcohol, while those with depression do frequently. However chronic anxiety associated with ME/CFS will deplete energy further, contribute to faintness, cognitive difficulties and increased respiration.

He then talked about appropriate investigations. The basic blood workup should be done as for all fatiguing illnesses and these are sufficient to exclude other causes for chronic fatigue in the majority of patients. Things to add in depending on history and symptoms may be: ANA, CK, calcium, magnesium, tests for Addisons and on rare occasions infection serology (Lyme, viral) and neurological abnormalities (MRI, fMRI, PET scans). Other tests that are occasionally considered include tilt table, ECG monitoring and neuropsychological tests. Unfortunately in the UK searching for triggering infections, such as viral, bacterial (incl spirochaetes), protozoa and fungi (no evidence for involvement of candida) is rarely rewarding in terms of offering specific therapeutic options. History of immunisations on rare occasions may suggest a possible trigger and there is recent controversy about the HPV vaccine.

Quite often it is a difficult question of how far to delve into issues such as life events, stress, physical injuries, environmental toxins and childhood trauma as there is at least some evidence that they may all play a cofactor role in precipitating ME/CFS. He then discussed the importance of the control population in ongoing ME/CFS research. Although the ideal control group would be family members this is often difficult and perhaps monitoring people with ME/CFS through several periods of relapse and remission would be best way forward.

Sonya Marshall-Gradisnik and Don Staines (Griffith University, Gold Coast, Australia) presented their work on biomarkers in ME/CFS. They had had two recent papers published – and The two researchers highlighted these papers are from a series of papers that will be released in the coming months. These two papers discussed this important work on single nucleotide polymorphisms (SNPs) in both transient receptor potential (TRP) ion channel genes and acetylcholine (AChR) receptor genes. TRP and AChR are part of the ancient or innate immune system. The TRP ion channels respond to environmental threats, temperature, chemicals etc. They are distributed throughout virtually all cells of the body. The range of threats may lead to widespread symptoms. Imposed physical activity is the wrong thing to be doing as it will likely exacerbate adverse signaling in patients expressing these SNPs. Acetyl choline is a major neurotransmitter seen throughout the entire peripheral, autonomic and central nervous systems and is also part of the non-neuronal signaling mechanisms of the ancient immune system. SNPs may cause change in protein structure of translated protein and therefore possibly change in function of these ion channels or receptors. 280 people were recruited and screened using the CDC criteria and exclusion criteria. 115 had ME/CFS, 90 were non-fatigued and 75 were excluded. Those included were given questionnaires (SF36, FSS, KPS), and included housebound patients. Bloods were taken for testing. 13 SNPs were associated with ME/CFS compared to controls (9 – TRPM3, 2 – TRPA1, 2 – TRPC4). TRPA1 is activated by exogenous and endogenous inflammatory agents, leading to pain and inflammation. It regulates neuropeptides and is a multiple chemical receptor. It is associated with changes in neuropeptide receptors and inflammatory cytokine profiles. TRPM3 is located on the pancreaticβ cells and in the CNS. It is associated with pain. TRPC4 is associated with vasomotor function and smooth muscle function. 17 SNPs were associated significantly with AChRs in ME/CFS patients (9 – mAChM3, 5 - nACh alpha 10, 1 -AChR alpha 5 and 1 - nAChR alpha 2 Collectively, AChR and TRP SNPs likely influence the gastrointestinal tract involving insulin and glycogen secretion, B and T lymphocyte development and proliferation, and neurological systems associated with sleep, pain and arousal. This research highlighted the possible role of TRP ion channels and AChRs in the onset of ME/CFS.

Next Generation:
A panel discussion then ensued involving 4 new student researchers, and it was good to hear their involvement, which bodes well for the future.

The students were -

  • Bharat Harbham (UEA/IFR)
  • Fane Mensah (UCL)
  • Navena Navaneetharaja (UEA/IFR)
  • Daniel Vipond (IFR)

Jo Cambridge (London, UK) then talked about B cell biology and ME/CFS. She gave some background history explaining that Rituximab had been used in 1998 to treat Rheumatoid Arthritis and SLE. The work of Mella and Fluge then further drove the hypothesis that B cell depletion could be implicated in ME/CFS. Her group looked at B Cell biology, biomarkers for response and relapse and other B cell directed therapies. The B cell has a large number of markers. Markers tell the age of the cell and other expressions. Every new B cell has a different receptor. Adherence is involved. B cells move through plasma cells to make antibodies. Antibodies are a form of B cell receptor, and are released onto surfaces, and bind to help clear macrophages from the body. They are made in the bone marrow and circulate to lymphoid organs. Antibodies recognize the different stages on the target bug. (e.g. antigen). IgM, IgA, IgG are all a different shape, all recognize the same antigen, but bind to cells in different ways. In a normal immune response, IgM is apparent in the first 7-10 days, then IgG. Memory B cells also form to attack recurrent bugs. There is interaction with T cells causing cytokines to help B cells make the antigen.

Cytokines interleukin8 and interleukin5 are elevated in ME/CFS and interleukin23 is down. There are also early and late effects in this illness leading to different cytokine levels. Antibodies in disease can form to “self” giving rise to immune complexes lodging in tissues leading to inflammation (e.g. lupus, rheumatoid arthritis). The antibodies bind and damage or change cell function. They can interfere with communication between cells.

Rituximab works in diseases where there are antibodies, leading to B cell depletion by recognising CD20 on the B cell. This in turn leads to B cell destruction in the circulation. B cells can regenerate. Changes occur in levels of Anti CCP after a single rituximab course. It is very complicated.

In ME/CFS there were positive results from use of rituximab in Norway. Patients do differ and there is no clear picture of the B cells. The B cell phenotype can be compared to the ME/CFS demographics using flow cytometry. One can look at complex things such as maturation, plasma cells, percentage of B cells in the blood, associated demographics, percentages of memory and naïve B cells etc.

CD24 is present on B cells associated with maturation (mainly on young cells). CD38-CD21 – memory B cell subsets – high expression in controls, less so in ME/CFS. Duration of illness gives different levels, with B cells normalizing over time. There are no differences in classical B cells.

Immune brain communication and relationship to inflammation induced fatigue were discussed by Neil Harrison (Sussex, UK). He outlined the symptoms associated with sickness behavior and listed the behavioural changes that occur to protect the body. He explained how cytokines injected into rodents led to symptoms of sickness behavior. Humans given high doses of interferon-α to treat Hepatitis C also develop sickness behavior and often experience severe fatigue. There is immune-brain communication via a number of pathways, and in particular via the vagus nerve. The microglia are also activated leading to brain inflammation.

Typhoid vaccine was used as a bacterial mimic. The fMRI showed activity++, and PET showed increased metabolism particularly within immune-brain communication pathways. Inflammation induced insular activity, which predicts fatigue. Interferon mediated fatigue is a side effect of interferon-α therapy (a viral mimic). MRI scans were done before, and shortly after beginning Interferon-alpha therapy then patients followed up for their 6-month duration of treatment. A challenge with IFN lead to the onset of fatigue and MRI changes within 3 hours. One could also use changes observed on MRI to predict which patients would subsequently develop the worst fatigue during their 24 weeks of treatment. There are implications for post-IFN fatigue and post viral fatigue. He asked the question “Do structural brain abnormalities persist post-inflammatory challenge?”.

John Chia (California, USA) updated us on his work with enteroviruses. He explained that there are many illnesses associated with enteroviruses. Most doctors are not trained to diagnose enterovirus infection. They are difficult to recognize. In 1995 41% CFS patients had positive serum enterovirus. He presented his research up to the present. He worked initially with blood samples, but moved onto tissue samples. In patients with persistent gastrointestinal symptoms, there was no evidence of H Pylori. But there were positive abdominal tender points, and focal gastritis on endoscopy (often mild).135 out of 165 patients were positive for VPI within the parietal cells, compared to 7 out of 34 controls. He tried to culture the viruses, but none survived. In 2008, viruses were found in biopsies (Enterovirus capsid protein) 81% showed VPI and 91% dRNA. Work with SCID mice showed effects of enterovirus infection after injection. (66% positive compared to 10% controls). He says that initial infection in the stomach is not controlled by the immune response. Enteroviruses travel via the vagus to the brainstem.

Claire Hutchinson (Leicester, UK) had looked at visual processing in ME. She talked about how visual symptoms were commonly reported in the 63 patients studied, using questionnaires and free report of symptoms. She wanted to map anomalous visual behavior onto the visual pathway, and to provide evidence to support symptom reports. There was experimental for the existence of visual stress/pattern glare in 20 patients compared to controls, which may reflect cortical hyperexcitability. In a study looking at visual attention and the ability to ignore background information (29 patients, 29 controls), found basic visual processing speed was normal, but both divided attention and selective attention were slow. She also presented data showing that, under some conditions, eye movements are less accurate in people with ME.

Betsy Keller (Ithaca,USA) went through activity guidelines to avoid symptom flares. This was an active talk incorporating audience participation. She talked about energy currency and post-exertional malaise (PEM), describing short term anaerobic, long term anaerobic and aerobic stages (>2 minutes) - the latter not being suitable for a person with ME/CFS because this energy system fails to recover normally. She described the abnormal recovery response, with ME/CFS patients taking 3 days or longer to recover from 5-10 minutes on a treadmill. PEM is the defining quality of this illness. It is easier to avoid it than to recover from it. Her advice is to pre-empt PEM with scheduled rest periods, do not wait for a crash, pace carefully, know your triggers and avoid or minimize them. Exercise should be redefined with focus on quality of life and use of the short-term energy systems that do work. Yoga and Tai Chi are suitable forms of exercise. The strategy for physical activity should use functional movement that is restorative, with a goal to improve. Aim should be to use the anaerobic energy systems with a work/rest ratio of 1:3, 1:4 or more if needed. That is, ‘work’ for 30 seconds, recover for 90 seconds (1:3).

She went on to explain the importance of core stability to conserve energy. The core includes muscles, bones, connective tissue of the trunk from the neck to hips- it connects the extremities. She explained the weight of the head and how it increases if one slouches (using extra energy unnecessarily). Warm up should begin with focused, square or nose-breathing (4 sec inhale, 6-8 exhale). This will often help symptoms too by better oxygenating the tissues.

5 steps to align core:

1) Contract pelvic floor (contract muscles that stop flow of urine or Kegel),

2) draw in umbilicus (draw belly button toward spine),

3) raise ribcage (rib cage points up toward ceiling or umbrella diaphragm).

4) Lift shoulders up to ears then back and let drop down,

5) retract chin. (Some of these exercises can be done lying down). Back extension is important (lying on floor on belly).

She then ran through some exercises on the floor or Swiss ball straightening arms and legs - alternate and opposite sides. These exercises strengthen the core. It is important to assess how one feels the next day to determine if the work/rest ratio is sufficient. If structured activity works, core stability improves, movement becomes more efficient and less energy draining. Activities need to be monitored and modified. The exercises should be very brief e.g. 30 seconds of activity, 90 seconds of rest, 3 times. The heart rate (HR) can be monitored and should not exceed the anaerobic threshold, and watch to see which exercises work at what HR. There is a perceived exertion scale and the aim should be to stay at the bottom level.

She described structured activity as empowering, improving quality of life, giving a sense of control and being off the rollercoaster. Energy conservation involves pacing, body position, joint protection and activity planning. There is need to think circularly not linearly (use a work/rest ratio all day), acknowledge limitations, aim for core stability and structure physical activity. She then outlined 10 simple energy-saving tips shared with her by Staci Stevens of the Workwell Foundation: Make bed while you are in it or not at all Take things around the house in a back pack. Shower sitting down Simplify clothes and hair Use an answering machine Pack groceries smartly ready for unpacking Cook ahead Get disabled car park Prioritize chores Learn to say No and Yes

Olav Mella (Bergen, Norway) brought us up to date discussing the Phase 2 and 3 studies of the rituximab trial. The Phase 2 study will be published shortly. 20% patients had a transient worsening of symptoms. There was marked improvement of physical function in 6 of 9 previous placebo patients. Half of the original responders were still responding at the end of follow up (36 months). The quality of life of the responders was very good. Only 5 patients were as low as 30%. During the trial levels of function were tested using a bicycle on a ramp. Experience with measuring endothelial dysfunction was gained. Maintenance therapy may sustain response

A new study is now underway. Patients recruited have been ill for 2-15 years. The Canadian criteria were used for diagnosis. 4 university hospitals and a community hospital were involved. Patients were given information and filled in the De Paul questionnaire. Biobank material was withdrawn and frozen. Patients undergoing the ramp test may need to wait 3 months before start of treatment to get back to their normal level. The study is randomized, double blinded, placebo-controlled. Study period will be 24 months, so results will be available in summer 2017, unless there are serious side effects. There will be no access to randomisation. All monitoring will be external. The physicians concerned will not see the patients. Rituximab 500mg/m2 will be given on days 0 and 15, and then 500mg at 3, 6, 9 and 12 months. Patients will monitor themselves. SF36 will be used every 3 months and FSS at zero, 6, 12, 18 and 24 months. Electronic activity will be assessed at zero and 18 months, using a wrist band. Blood samples will be drawn regularly for biobank freezing.

The primary endpoint will be the level of fatigue over 24 months. The secondary endpoint will be changes in QOL, and any effects of toxicity.

Sub-studies will include endothelial dysfunction (large vessels - ultrasound and microvessels - PORH analysis) – Is there correlation between endothelial dysfunction and ME and improvement parallel to endothelial dysfunction? Ergo spirometry can be used, if patient is able, to see if there are changes in the anaerobic threshold.

Another sub-study will look at gastro-intestinal function.

These are high quality studies hoping for good clinical response. One must expect up to 20% placebo response, and hope for a 50% rituximab response. One needs to look at clinical characteristics of the responders. There may be a 4-5 month delayed response. The biobank will be useful. There may be political impact. Another multicenter trial elsewhere is needed. Toxicity also needs to be considered. Some patients cannot tolerate the treatment.

A further new study using cyclophosphamide started in March 2015. This is a cheaper immune-modulating drug. It shows major improvement in treatment for breast cancer. 40 ME patients have been recruited with 6 infusions to be given every 4 weeks. There are 3 groups of patients: those not treated with rituximab, previous non-responders to rituximab and those who have recurred after rituximab. Patients with mild to moderate illness are recruited and the trial will last 2 years. It does not include young patients or those at risk of pregnancy. It will be tried later on for 20 more severe patients.

The conference concluded with thanks to all speakers and closing remarks from Dr Ian Gibson and Invest in ME, and all agreed it had been the very best yet.

I would like to thank Invest in ME and ANZMES for making it possible for me to attend this excellent event.

Rosamund Vallings MNZM, MBBS

Conference DVD

C10 Conference DVD

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The DVD contains 4 discs and is in PAL format- and contains the full presentations from the 2015 conference plus plenary sessions, and the pre-conference dinner keynote speech by Mike Shepherd.

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DVD Details

Format: PAL
Length 437 minutes
Contents Full presentations from conference plus pre-conference dinner speech

The views expressed at the Invest in ME International ME Conference conferences by the presenters and delegates to the conference and any information material distributed are their own personal opinions that are not necessarily shared or endorsed by the Trustees of Invest in ME/Invest in ME Research.

Invest in ME/Invest in ME Research accept no responsibility for the views expressed or any subsequent action taken. The contents of any presentation should not be deemed to be an endorsement, recommendation or approval of such content by Invest in ME/Invest in ME Research. The materials presented at the 1st Invest in ME International ME Conference 2006 do not constitute medical advice. No medical recommendations are given or implied by Invest in ME/Invest in ME Research. Any person registering or attending an Invest in ME/Invest in ME Research conference, or purchasing the DVD, who may take any action or consider medical treatment or referrals should take detailed advice from their own medical practitioner. Invest in ME/Invest in ME Research disclaims any implied guarantee about the accuracy, completeness, timeliness or relevance of any information contained at the conference.

By purchasing any of the conference DVDs you agree that Invest in ME/Invest in ME Research is not liable for any complications, injuries, loss or other medical problems arising from, or in connection with, the use of or reliance upon any information contained in the conference.


Images from IIMEC10, London, 2015

Biomedical Research into ME Colloquium 5

IiME Research Meeting London, 2015

Invest in ME organised and hosted the Biomedical Research into ME Colloquium number 5 in May 2015.
Over sixty researchers from thirteen countries attended the two-day meeting.

This is now an important fixture in the research calendar and a unique event for ME.

Use this link to go to the BRMEC Colloquium page.


More details of previous Invest in ME conferences can be found on the current IIMEC* conference overview page - Click here.

Our Sponsors for IIMEC10

Invest in ME wish to thank the following organisations for helping to sponsor the 10th Invest in ME International ME Conference 2015.

The Irish ME Trust

The Irish ME Trust have sponsored a speaker at all of our conferences and we would like to thank them for their continued support. IMET have been a continual source of constructive change for ME in Europe. They were one of the founder members of the European ME Alliance. See also here

Sveriges RME

Invest in ME are very proud to announce that EMEA Sweden member RME (Riksföreningen för ME-patienter) made a donation to IiME to help sponsor the IIMEC10 conference. This underlined the great collaboration which has built up between IiME and RME and all our Swedish friends. IiME greatly value the collaboration with RME which will again see a number of the top Swedish researchers being involved in the BRMEC5 and IIMEC10 events in 2015. The magnificent work being performed by RME to encourage and facilitate biomedical research into ME in Sweden is proving to be beacon of hope for so many patients and will eventually be seen to be important part in eventually establishing the required research and treatment for ME.

Norges ME Forening

Norway's ME Association (Norges ME Forening) is sponsoring the IIMEC10 conference. Norges ME Forening has been a long standing supporter of IiME we are very grateful for this kind donation. NMEF have been trailblazers for change with regard to ME perception, treatment and awareness and it is no surprise that some of the most promising biomedical research into ME is being conducted in Norway.

Vitae International

Our thanks to Vitae International for being a sponsor of the IIMEC10 pre-conference dinner.
Vitae Natural Nutrition is a laboratory that develops natural products based on Science and nutraceutical technology, designed to activate, improve and regulate the biological processes of the body maintaining and extending its functions. See also here



Contact Us

Contact Us

If you have any questions regarding the conference then please contact us by email and we will get back to you as soon as possible. Thank you for your interest in the charity.

Contact Address

  • Address: Invest in ME Research PO Box 561 Eastleigh SO50 0GQ Hampshire UK
  • Phone: 02380 643736 / 07759 349743
  • Email:
  • Conference:
  • Centre of Excellence for ME:

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Other Invest in ME Research Activity

Invest in ME Research - Mainstreaming Research into ME

Invest in ME Research Projects

Research funded and facilitated by Invest in ME Research.

View the completed and ongoing projects made possible by the supporters of the charity.


IIMER are facilitating a strategy of biomedical research into ME. The charity is currently funding possibly important research projects for ME in the UK with international collaboration.
Currently the main hub of research is at Quadram Institute Bioscience and University of East Anglia ) in the Norwich Research Park and we also fund research at UCL. These involve a gut microbiota project in Norwich and B cell research in London.

Advisory Board

The IIMER Advisory Board is made up of eminent researchers who are helping the charity to form a credible and productive biomedical research strategy which will provide the best and quickest route for possible treatments and cures for this disease.

Centre of Excellence for ME

Translational biomedical research - an iterative feedback of information between the basic and clinical research domains in order to accelerate knowledge translation from lab to bedside and back to lab again - allows translation of findings in basic research more quickly and efficiently into medical practice to produce more meaningful health outcomes and facilitate the sharing of repositories and research-based facilities and laboratories. This is the model IiMER are attempting to promote in the proposal for an examination and research facility based in Norwich.

Let's Do It For ME

Let's do it for ME! is a patient-driven campaign to raise awareness and vital funds for a UK centre of excellence for translational biomedical ME research, clinical assessment, diagnosis and treatment for patients, training and information for healthcare staff, based around the Norwich Research Park in the UK and aiming to work collaboratively with international biomedical researchers.

Research Colloquiums

In addition to the International ME Conference the charity also organises an annual International Research Colloquium which attracts researchers from around the world in order to discuss experiences and open up collaborations in order to find answers for this disease.

European Collaboration

Invest in ME Research is one of the founder members of the European ME Alliance (EMEA) – a grouping of charities and patient organisations working together across Europe. Now fifteen European countries collaborating.

Last Update 12/06/2016


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  • Address: PO Box 561 Eastleigh Hampshire SO50 0GQ

  • Phone: 02380 643736 / 07759 349743

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