Circulating microRNAs as biomarkers in MND; version 1.0
Research type
Research Study
Full title
Characterisation of circulating microRNAs as diagnostic and prognostic biomarkers for Motor Neurone Disease (BioMND).
IRAS ID
216732
Contact name
Suresh Kumar Chhetri
Contact email
Sponsor organisation
Lancashire Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
Research Summary
Motor Neurone Disease (MND) is an incurable disease that causes progressive wasting and weakness of muscles involved in movement, speaking, swallowing and breathing. Most patients die within five years of symptom onset. At present there is no specific test for MND, with diagnosis relying on the recognition of typical features by doctors and exclusion of a number of other conditions. The lack of diagnostic test or disease signatures (biomarkers) can result in substantial delays in diagnosis as well as potential for diagnostic errors, and has implications in accessing appropriate care and management.
It is well recognised that small molecules called microRNAs regulate the expression of different proteins within cells, influencing how each cell grows and functions. These microRNAs may remain inside the cells in which they are produced, or may be released into the circulation to influence surrounding cells and tissues (‘circulating microRNAs’). It has been shown by us and others that the patterns of microRNAs in the biofluids (e.g. blood) of patients with various conditions, including brain tumours, are altered compared to those of healthy counterparts. Thus, they have the potential to act as biomarkers for diagnosis.
A few recent studies have shown that the expression of microRNAs within tissues can be altered in patients with MND, but the relevance of these altered patterns is unknown. Based on these initial studies, we think that alterations in microRNAs will also show a distinctive pattern in the biofluids of patients with MND. We will therefore collect blood samples from patients with MND and from age- and sex-matched healthy individuals, and screen these samples to reveal their specific microRNA signatures.
It is anticipated that this study will identify a unique panel of altered circulating microRNAs which will permit the development of a simple test for the early and accurate diagnosis of MND.
Summary of Results
Motor Neurone Disease (MND) is a fatal neurodegenerative disease characterised by the degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and anterior horn cells of the spinal cord. There are no diagnostic tests for MND, and the diagnosis is based on typical clinical findings. The lack of diagnostic tests or biomarkers leads to significant diagnostic delays.
MicroRNAs (miRNAs) are small, non-coding RNA molecules 18-25 nucleotides in length. These miRNAs are not only expressed in cells and tissues but are also released into the circulation and can be detected in bio fluids such as serum, cerebrospinal fluid and urine. A few recent studies have shown that the expression of microRNAs within tissues can be altered in patients with MND, but the relevance of these altered patterns is unknown.
The aim of this pilot study, undertaken as a student project, was to investigate microRNA expression profiles in MND and identify a panel of altered circulating microRNAs that may prove to be potential signatures/biomarkers for diagnosis of MND.
Data from this initial pilot study, showed no significant dysregulation of circulating miRNA in patients with MND. However, the study sample was very small and other factors including co-morbidities, duration of illness, disease type and severity were not factored at the time of sample collection. Therefore, the results should be interpreted with caution, given the positive signals from other studies. Further large-scale high-quality studies using standardised test methodology would be important to evaluate the potential of miRNA as diagnostic and/or prognostic markers in MND.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
17/EE/0249
Date of REC Opinion
17 Jul 2017
REC opinion
Further Information Favourable Opinion