Markers of disease progression
There is currently no diagnostic test for MND and no specific ‘biomarker’ to monitor the disease. These projects aim to find a marker of disease progression to speed up diagnosis, prognosis and disease monitoring of MND. Read the latest news on biomarkers in MND on our MND Research blog.
An asterisk (‘*’) next to a title marks the research projects that directly involve animals.
Principal investigator: Prof Linda Greensmith
Associated researchers: Dr Andrea Malaspina, Prof Eran Hornstein, Prof Elizabeth Fisher, Dr Pietro Fratta, Prof Adriano Chio, Dr Johnathan Rohrer and Dr Anna Coenen-Stass
Institutions: University College London, Queen Mary University, Weizmann Institute of Science and University of Torino
Start date: January 2016
End date: December 2018
The development of a biomarker for MND is of upmost importance in diagnosing and monitoring disease progression. Previous research has suggested micro RNAs (miRNAs) present in the blood may be used as a biomarker. miRNAs are short forms of RNA, the cell’s copy of our genetic material DNA, that are found to be stable in the blood. This project aims to observe changes in miRNA within a large set of already collected patient samples and also in mouse models of MND. The researchers will also test a potential drug that has been previously shown to normalise miRNA levels.
Associated researchers: Dr Paul Skehel, Prof Thomas Gillingwater and Dr Cornelia Roesl
Institution: University of Edinburgh
Start date: January 2016
End date: July 2018
Diagnosis of MND is usually made after a number of diagnostic tests have been performed. This includes investigation of the health of the connections made by motor neurones at the neuromuscular junction using EMG or muscle biopsy – a highly invasive and painful procedure. This project aims to develop a different approach called confocal endomicroscopy. This non-invasive approach uses a probe (only 1.5mm in diameter), which is applied to the surface of the muscle. This probe is also connected to a powerful microscope, enabling live observation at the neuromuscular junction. Already tested in mice, the researchers aim to develop this technique towards the clinic to enable an earlier diagnosis of MND.
Associated researchers: Prof Nigel Leigh, Prof Sarah Newbury, Prof Martin Turner and Dr Greig Joilin
Institutions: University of Sussex and University of Oxford
Start date: April 2016
End date: August 2018
There are currently no robust biomarkers of diagnosis and disease progression in MND, with diagnosis being based on clinical examination. This project will use a new method for cataloguing a group of molecules called non-coding RNAs in the blood and cerebral spinal fluid (CSF) of people living with MND and healthy individuals. Ten of the most promising non-coding RNAs, which show changes in the blood and CSF samples from people with MND will then be validated as potential biomarkers in order to provide an earlier diagnosis and monitor disease progression.
Associated researchers: Dr Andrea Malaspina and Prof Dame Pam Shaw
Institutions: University of Oxford, Queen Mary University and University of Sheffield
Start date: August 2016
End date: July 2021
In order to diagnose MND faster, we need to better understand the causes of the disease. One way to do so is to identify the unique fingerprints – MND biomarkers – by obtaining biological samples from people with MND. Over the span of five years, this study will collect blood, urine and skin cells from 900 people with MND as well as from over 400 people without the disease. We are also seeking to identify biomarkers that predict how MND progresses, and why people with MND progress at different rates. This has important implications for clinical trials. The blood and urine samples will be subjected to an extensive analysis to search for chemicals that might act as MND biomarkers. The skin cells will be reprogrammed into motor neurones using an iPSC technology and used to test the effects new drugs can have on motor neurones, exploring the possibility that different drugs may work for different subtypes of MND. The extensive collection of samples will also act as a resource to future researchers investigating MND.
Institutions: University of Sheffield and University College London
Start date: November 2016
End date: October 2019
This project is complementary to the AMBRoSIA programme, which aims to identify biomarkers for diagnosing MND and monitoring its progression more accurately. We know that MND progresses at different rates, and so we hope that it will be possible to identify biomarkers that characterise subgroups of MND too. The NECTAR project will use the blood samples collected as part of the AMBRoSIA programme and conduct genetic analysis on these samples, looking for genetic mutations and variations known to be linked to MND. The results of these analyses will be used for research, to see if there are specific biomarkers that characterise the genetic forms of MND. There will also be the option for the person with MND, their families and future family members to find out the results of their genetic analysis – in other words, whether they are carriers of MND-related genes.
Institution: Imperial College London
Start date: August 2017
End date: November 2018
Finding MND biomarkers (ie fingerprints) is crucial to diagnose a patient faster and to reliably track MND progression over time. By establishing a measure that would reliably inform us about the presence of MND and its current stage, researchers can use it in clinical trials to observe improvements after taking a specific drug. Dr Sibley and colleagues identified a specific molecule that they believe is present at abnormal levels in about 98% of people with ALS, the most common form of MND. This project will focus on further investigation of this molecule, which could eventually lead to a development of a new biomarker.
Principal investigator: Prof Martin Turner
Institution: University of Oxford
Award: £240,013 (Total amount: £1,600,089)
Start date: August 2013
End date: August 2018
Biomarkers in Oxford (BioMOx) is a research project with the aim of identifying a diagnostic and prognostic biomarker for MND. Advanced MRI brain scans and analysis of spinal fluid and blood have revealed several biomarker candidates, and shown that their combination improves accuracy. This project will test these in people who are at risk of developing inherited MND, particularly in those with the C9ORF72 mutation. The aim of this project is to identify a biomarker for MND and enable more efficient organisation of clinical trials, as well as effective care-planning.
Update: This project is now recruiting people who are at risk of developing inherited MND (known as pre-symptomatic) to take part. To find out more please visit www.mndassociation.org/biomox.
Principal investigator: Dr James Bashford
Associated researchers: Prof Chris Shaw and Prof Kerry Mills
Institution: King’s College London
Start date: October 2016
End date: September 2019
Muscle fasciculations (‘rippling’ of a muscle under the skin) are a common symptom of MND. So far, muscle fasciculations have been measured by inserting a fine needle into muscles, a procedure which can be very painful. In this project, Dr Bashford will use a much less invasive technique called surface electromyography (EMG) that allows measuring fasciculations from electrodes placed on the skin. Fasciculations will be recorded from arms and legs of people with MND at multiple stages within 12 months to observe changes over time. These will then be compared to the patients’ muscle strength to track the progress of the disease. The results of this study will help to better understand the role fasciculations play in MND. Moreover, the use of surface EMG might also be used to help test potential new therapies in the future.
Principal investigator: Dr Matt Gabel
Associated researchers: Prof Nigel Leigh and Prof Mara Cercignani
Institution: University of Sussex
Start date: July 2017
End date: June 2019
Researchers are developing a range of ways to measure how MND progresses over time. These might be to identify a set of chemicals where their levels change in the blood or in the cerebrospinal fluid (the fluid that surrounds our brain and spinal cord). Another method that researchers are working on is to look at the change in patterns in brain scans over time. Until recently, no-one has looked at how these measures of disease progression compare against each other. In his PhD project, Matt Gabel applied a mathematical model to look at all the data to see the overall sequence of events. For example, were changes in a brain scan seen before changes in the chemicals in blood? In his fellowship he will build on these ideas to confirm whether or not this mathematical model works, using data from people with MND from international collaborators.
Last updated: 1 October 2017