MEA to fund new research into biomarkers and markers of disease activity in people with severe ME/CFS | 20 December 2016

We are pleased to announce that – following the normal rigorous peer review procedures – the MEA Ramsay Research Fund has agreed to fund a study that will be examining what are termed microRNA profiles in peripheral blood mononuclear cells (PBMCs) and exosome-enriched vesicles.

The study will involve the use of ME Biobank blood samples that have been obtained from people with severe ME/CFS and from our Biobank group of healthy controls.

The research will be carried out by Professor Elisa Oltra and colleagues in Spain and we are hoping that there will also be additional UK collaboration to the involvement of the ME Biobank in supplying the samples.

The study will start early in the New Year and will take 12 months to complete.

Total RRF funding = approx £50,000

6b28decf408241708ae5497b815b026f.jpg.200x200_q95_crop_detail_upscaleFind a brief CV for Professor Oltra HERE.

 
 
 
 
 
 
 
 


DR CHARLES SHEPHERD, MEDICAL ADVISER TO THE ME ASSOCIATION, COMMENTS


Elisa Oltra, who is Professor of Cell and Molecuar Biology, and her colleagues at the Catholic University of Valencia in Spain have a well established biomedical research facility for this type of work and the group has developed an international reputation in this complex area of scientific investigation at a cellular level

They have an interest in both ME/CFS and fibromyalgia and have been using these new technologies to investigate the role of miRNAs in fibromyalgia – see paper below

Professor Oltra gave a presentation on this work at the 2016 Invest in ME conference – see conference report here:

www.meassociation.org.uk/2016/06/iime-conference-another-important-day-for-sharing-ideas-on-research-20-june-2016/

In very simple terms:

A microRNA (abbreviated to miRNA) is a small regulatory protein molecule that is found in plants, animals and some viruses. It has regulatory functions including the regulation of gene expression – how genes express their functions.

The discovery and study of miRNAs has opened up the possibility of developing new ways of helping to objectively diagnose a long list of diseases, including ME/CFS, autoimmune and neurological illnesses. This research will aim to build up a detailed picture of possibly diagnostic changes in miRNA profiles in ME/CFS – as has been found in fibromyalgia.

The study will profile miRNA expression in what are termed exosome-enriched fractions and compare the results to those in peripheral blood mononuclear cells (PBMCs)

Screen Shot 2016-12-20 at 13.02.14 copyHere’s a diagram of MicroRNA and a brief explanation.
 
 
 
 

Exosomes are extracellular vesicles which act as long-distance cell-cell communication vehicles

Screen Shot 2016-12-20 at 13.05.02Exosome Image

Peripheral blood mononuclear cells (PBMCs) are defined as any blood cell with a round nucleus (i.e. a lymphocyte, a monocyte, or a macrophage). These blood cells are a critical component of the immune system and are involved in fighting infection and adapting to intruders. The lymphocyte population consists of T cells, B cells and Natural Killer cells.
 
 
 

Screen Shot 2016-12-20 at 13.07.15 copyPBMC Image

Using blood samples from people with severe ME/CFS in the ME Biobank, the study will be examining the miRNA profiles in people with severe ME/CFS and comparing the results to those in a group of matched samples from healthy controls in the ME Biobank.

The aim is try and find miRNA profiles that could serve as both diagnostic and sub-grouping biomarkers, as well as biomarkers of disease severity and biomarkers that could be used to objectively measure the effect of treatment.

The findings from this research could also reveal alterations in key cellular pathways that may then lead to new approaches to the drug treatment of ME/CFS.


RELEVANT PUBLICATION FROM PROFESSOR OLTRA RELATING TO THIS RESEARCH


From PLoSOne, 24 March 2014

Identification of a microRNA signature for the diagnosis of fibromyalgia.

Cerdá-Olmedo G, Mena-Durán AV, Monsalve V2, Oltra E3
Facultad de Medicina, Universidad Católica de Valencia “San Vicente Mártir”, Valencia, Spain, Cátedra Umivale en innovación e investigación en patologías del trabajo, Valencia, Spain

Abstract

BACKGROUND

Diagnosis of fibromyalgia (FM), a chronic musculoskeletal pain syndrome characterized by generalized body pain, hyperalgesia and other functional and emotional comorbidities, is a challenging process hindered by symptom heterogeneity and clinical overlap with other disorders. No objective diagnostic method exists at present. The aim of this study was to identify changes in miRNA expression profiles (miRNome) of these patients for the development of a quantitative diagnostic method of FM. In addition, knowledge of FM patient miRNomes should lead to a deeper understanding of the etiology and/or symptom severity of this complex disease.

METHODS

Genome-wide expression profiling of miRNAs was assessed in Peripheral Blood Mononuclear Cells (PBMCs) of FM patients (N=11) and population-age-matched controls (N=10) using human v16-miRbase 3D-Gene microarrays (Toray Industries, Japan). Selected miRNAs from the screen were further validated by RT-qPCR. Participating patients were long term sufferers (over 10 years) diagnosed by more than one specialist under 1990 American College of Rheumatology criteria.

RESULTS

Microarray analysis of FM patient PBMCs evidenced a marked downregulation of hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p (4-fold or more). All but the mildest inhibited miRNA, hsa-miR-21-5p, were validated by RT-qPCR. Globally, 20% of the miRNAs analyzed (233/1212) showed downregulation of at least 2-fold in patients. This might indicate a general de-regulation of the miRNA synthetic pathway in FM. No significant correlations between miRNA inhibition and FM cardinal symptoms could be identified. However, the patient with the lowest score for mental fatigue coincided with the mildest inhibition in four of the five miRNAs associated with the FM-group.

CONCLUSIONS

We propose a signature of five strikingly downregulated miRNAs (hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p and hsa-miR145-5p) to be used as biomarkers of FM. Validation in larger study groups is required before the results can be transferred to the clinic.


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