By Russell Fleming, Content Manager, ME Association.

ME Association trustees and staff were over the moon when we heard that the CureME team at the London School of Hygiene and Tropical Medicine had received a new grant of $2.1 million from the National Institutes of Health (NIH) in America.

The funding represents the biggest ever single investment in biomedical research to happen in the UK and it will enable a current project, that is searching for disease biomarkers, to be extended for another 4 years – until 2021.

The project is a longitudinal study that is measuring changes in the immune system and genetic profile of individuals in a disease whose symptoms are known to fluctuate over time. The initial £1 million project, which began in 2013, was over 3 years and had also been made possible by funding from NIH.

Dr Luis Nacul, who leads the CureME team, is also responsible for overseeing the UK ME/CFS Biobank, which has been built and maintained by charity support and the funding from America.

The new grant will enable the Biobank to increase in size as even more blood samples and clinical data will be collected from people with ME/CFS, multiple sclerosis, and healthy controls, and then made available to research applicants.

“The new grant from the NIH (US) will enable, for the first time, comprehensive prospective assessments of cases of ME/CFS at regular intervals. “This greatly enhances the chances of a breakthrough in the understanding of the pathophysiology of this complex disease and the identification of much-needed biomarkers for the diagnosis of different sub-groups of patients. “We very much look forward to continuing our partnership with the patient community, which has been key to the success of our research so far.” Dr Luis Nacul, Principle Investigator, CureME team, LSHTM.

The Biobank is the only resource in the world able to include samples from those most severely affected – the house- or bed-bound – and is the premier resource outside the United States for the study of the disease. All participants are examined by a clinician and must conform to the Biobank’s rigorous protocols.

The ME Association has been a long-time supporter of the Biobank and provides funding to support its development. This longitudinal project, that in total will amount to some £2.56 million, represents one of the most exciting opportunities to learn more about this devastating disease.

Dr Charles Shepherd, Hon. Medical Adviser to the ME Association, and Chair of the UK ME/CFS Biobank Steering Group, commented:

“This is a significant and vital sum of money that will help scientists unravel the mysteries of this devastating illness. “The irony is that the funding comes once again from America. “What this seems to suggest is that the USA is far more serious about finding the underlying causes of M.E., while the UK seems most willing to invest in inappropriate studies using cognitive behavioural therapy and graded exercise. “The fact that the NIH has decided to provide another major grant is an important endorsement of the ME/CFS Biobank, and we would like to congratulate all the staff who have been involved in setting up and developing what has become a vital new part of biomedical research infrastructure here in the UK. “We hope that other research groups will also now start to make use of this unique resource to achieve desperately-needed breakthroughs into the cause and treatment of ME/CFS.” Dr Charles Shepherd, Hon. Medical Adviser, ME Association,

Chair of the UK ME/CFS Biobank Steering Committee.

Research: A longitudinal immunological study for ME/CFS biomarker discovery

What are the UK ME/CFS Biobank team proposing to do with this funding?

They will be studying 110 ME/CFS cases (half severe, half mild-moderate) meeting all of the CDC, Canadian Consensus, and Institute of Medicine, criteria.

They will focus on detailed immunological and clinical phenotypes (subgrouping patients by immune differences, such as the number of different immune cells and cytokines, and clinical differences, such as severity).

Analyse inter-relationships (the relationship between the immune differences and differences in severity/symptoms and changes over time).

Cases will be assessed every 6-12 months, over 5 time points, to record changes in biomarker expression and link these to clinical parameters (whether their condition has gotten better, worse or remained stable) in order to analyse biomarkers at different stages of disease progression and try to identify subgroups.

Cases will be grouped according to trends in symptom severity using scores relating to pain, fatigue and functional status.

In-depth Immunological Profiling (to try and identify biomarkers) will involve: Phenotyping Lymphocytes (T cells, B cells and NK cells) and monocytes from the blood samples. Measuring the functional response of NK (natural killer) and T cells after stimulation (by a virus, for example). Analysing secreted cytokines from the stimulated NK and T cells. Genotyping the donors for MHC class 1 (molecules that trigger an immune response to a specific toxin or foreign substance) and KIR (recognise MHC class 1 cells and activates the killing response of NK cells).

They then want to determine whether changes in immune parameters come before, after or predict the changes observed in clinical presentation (changes in symptoms and severity over time).

This will be done by quantifying correlations between immunological biomarkers and by identifying biomarkers associated with changes in ME/CFS clinical status.

Significance of the study

“This study is unique for its strict inclusion criteria and detailed clinical phenotyping, adding specificity and validity to our analysis.”

“This is, to our knowledge, the first long-term prospective study of ME/CFS to incorporate both ambulatory and severe cases and to include comprehensive clinical data and in-depth immunological profiling.”

“This research will contribute to the development of better diagnostic tools and treatments.”

“The inclusion of severe cases through home visits will allow for research on a subset of patients often neglected in ME/CFS studies.”

“Because 1- 2.5 million Americans have ME/CFS, this study has the potential to improve the lives of a large patient population in the U.S. as well as advance the state of the field in the U.S. and internationally.”

“Patients and stakeholders are involved in all aspects of the research.”

More study information, here.

More Reaction

“This is great news for quality research into ME/CFS. The Biobank team has always put the needs of the patient first and it’s fantastic that their good work can now continue”

Cecilia Finnerty, Patient Representative.

“Such wonderful news for people with ME. It is a privilege to serve on the Steering Committee alongside a committed professional team who have such a heart for people with this illness.”

Hannah Clifton, Director, The ME Trust.

“ME Research UK is delighted that the team has been awarded a new grant from the NIH worth $2.1m. The funding will enable further research on those affected by ME/CFS over the next 4 years and will ensure that the UK’s first biobank of human blood samples continues to be a valuable resource for all researchers in the UK and beyond.”

Sue Waddle, Vice-Chair, ME Research UK.

“Congratulations to the London School of Hygiene & Tropical Medicine team for their grant award from the NIH. This is the most important development in UK research into ME this year and all the more so because it shows the international standing of the group. Very well deserved.”

Professor Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine, University College London

More Information

⇒ CureME announcement: ‘$2.1m investment is UK’s ‘biggest ever investment into physical causes of ME/CFS.’

⇒ Visit ME Association website for more information about the UK ME/CFS Biobank

⇒ Full details of the new grant from NIH

⇒ Details of the existing grant from NIH

⇒ More information about CureME at LSHTM