AMBRoSIA – our biggest ever research project

The AMBRoSIA (A Multicentre Biomarker Resource Strategy In ALS) project is our biggest, most ambitious research undertaking to date. The project funding began in August, closely followed by being the focus of this month’s ‘Make Your Mark’ fundraising appeal. Here we explain more about what this flagship project is all about.ambrosia-pic

This new five year research project, costing in excess of £2 million, will search for biomarkers of MND on larger scale than ever before. It will leave a legacy resource to improve diagnosis and our understanding of MND for the future.

AMBRoSIA will be nested in three world-class research centres in Oxford, London and Sheffield, and will be led by three of the UK’s top MND researchers – Prof Martin Turner (Oxford), Dr Andrea Malaspina (London) and Prof Dame Pamela Shaw (Sheffield).

Why do we need biomarkers?
A biomarker is a ‘fingerprint’ of MND – something that can be measured in the body that is unique to MND. Biomarker discovery would mean a faster diagnosis and a better understanding of the disease, which will lead to bespoke, effective treatments. You can read more about why biomarkers are so important in a previous blog.

The collection of good quality samples, from the same people over time, is at the heart of biomarker research – and that’s what AMBRoSIA is all about.

Who can take part?
AMBRoSIA will recruit 900 people with MND to take part. In addition, 450 people without the disease will also be recruited, for comparison (this is known as a control group). The control group will consist of 135 first-degree relatives of people with MND (a parent, sibling or child), and 315 people with no family link to the disease.

What samples will be collected?
Participants will donate blood, skin and urine samples on a regular basis. Where possible, cerebrospinal fluid will also be collected.

In total, it is expected that AMBRoSIA will collect over 250,000 samples across the five years of the project.

What will the samples be used for?
The samples collected will be stored across the three sites and will undergo a series of tests to search for biomarkers of MND. In addition, the skin cells will be used to create motor neurones using ground-breaking stem cell (iPSC) technology. You can find out more about iPSC technology on our website. Motor neurones created using iPSC technology will be used to screen potential new drugs.

Ultimately, the samples will form a new large-scale biomarker testing resource, which will be used to for future research.

How will the samples be analysed?
The lead researchers were all involved in the development of international consensus guidelines for the collection, processing and storage of samples of the highest possible quality. These guidelines will be used in the sample analysis for AMBRoSIA.

All the samples need to be processed using the same 'recipe'.

All the samples need to be processed using the same ‘recipe’.

The TV programme the Great British Bake Off illustrates the importance of developing guidelines for sample processing. Those of you familiar with the programme will know that even though the contestants may be given exactly the same recipe, their cake creations may turn out very differently! The researchers want the same results from using their ‘recipes’ in every centre!

What happens now?
The project is now in the crucial set-up phase. This includes setting up the structure of AMBRoSIA and its governing system, recruiting the scientists to work at each centre, and gaining the ethical approval needed to undertake the study. A Steering Committee is being formed, which will oversee the running of the project. This will comprise of research leaders, representatives from the MND Association and people living with MND.

How can I get involved?
As the study is still being set up, the researchers aren’t collecting samples yet. However, if you have MND you can let us know that you are interested in taking part by joining our research list.

When the researchers are ready to start collecting samples we will send out a letter to everyone on this list, explaining what to do next. There’s more information on the research list on our website. Please email us on our research@mndasociation.org email address if you would like to be added.

Defining disease progression in MND from MRI ‘snapshots’

Although conventional brain magnetic resonance imaging (MRI) scans are often normal in people with MND, more sophisticated MRI techniques have shown changes in the structure of their brains as the disease progresses. A limitation of even the most recent MRI techniques is that they can only provide a snapshot of the brain at a single moment in the course of the illness.

Only a description of how these MRI changes evolve over time as the disease advances will tell us how the nerve cell damage due to MND is evolving, area by area, in relation to an individual’s symptoms. This could be obtained by collecting several MRI scans from the same person over time, but the nature of MND makes it challenging to get scans showing the course of disease over several years.

We are funding a three year PhD studentship that aims to use a new imaging method to define the progression of MND (our reference: 859-792). The researcher team, involving Profs Mara Cercignani and Nigel Leigh from the University of Sussex, will use MRI scans that have already been obtained from people with MND and healthy controls. Continue reading

Using a new imaging technique to shed light on changes to nerve cells in MND

Magnetic Resonance Imaging (MRI) technology is advancing rapidly as a tool for diagnosing and monitoring disease. In MND, MRI scans are used to understand changes that happen to the brain because of this disease.

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Prof Nigel Leigh

Prof Nigel Leigh from the Brighton and Sussex Medical School (University of Sussex) is carrying out a study looking into changes to motor neurones using a new imaging method (our reference: 824-791).

Neurite Orientation Dispersion and Density Imaging (NODDI) is a type of MRI scan, and can see whether MND is affecting specific parts of motor neurones, called neurites, found within the brain. Neurites are the tiny parts of the nerve cells that branch out from the main body of the nerve cell, and are important in the functioning of the brain.

Prof Leigh and his team hope that the new imaging approach will tell us more about the sequence of events that cause motor neurones die, and how this relates to the symptoms of people with MND. Continue reading

Using surface EMG to see if fasciculations can be used as a biomarker for MND

What are fasciculations?

When motor neurones in the spinal cord become damaged this makes them electrically unstable, meaning they spontaneously discharge electrical impulses that cause small groups of muscles to contract. These contractions, known as fasciculations, are a common symptom of MND. Research suggests that they might be a good marker of motor neurone health.

Tracking fasciculations with surface EMG

Prof Chris Shaw

Prof Chris Shaw

Led by researchers Prof Chris Shaw and Prof Kerry Mills, Dr James Bashford is using technology called surface EMG to collect data on the site and frequency of fasciculations in different muscles in people with MND. Fasciculations in people with MND are different to benign fasciculations, which can occur in people without the disease and are generally harmless. James and the team hope to show that fasciculations in those with MND have a unique ‘fingerprint’ which can be accurately identified and tracked.

Data collected will be compared to other information currently used to track the progression of MND. James and the team hope surface EMG might provide a more sensitive way of measuring disease progression than previously used methods. This one year feasibility study is being carried out at King’s College London at a cost of £95,000 (our reference: 932-794). Continue reading

Developing ultrasound imaging as a potential non-invasive diagnostic tool for MND

When diagnosing MND, it is important to look at the activity and impact of the motor neurones themselves – is the electrical message being carried down the nerve properly, and is it reaching the end of the nerve in the muscle? Malfunctions in the electrical activity at the muscle end of the nerve cell result in the muscle twitching that many people with MND experience.

One of the tests used to diagnose MND is an electromyography or EMG test. It involves putting needles into a muscle to measure electrical activity. It can be a painful and unpleasant experience, which doctors and patients are only willing to do when necessary.

There is evidence that ultrasound imaging may be able to detect the same malfunctions in the electrical activity of muscle as EMG, by looking at the way the muscle behaves when electrical activity occurs. Ultrasound images produce the typical grey scale images, for example pictures from baby scans, and can be used to provide images of any muscles in the body. Continue reading

Investigating miRNAs as a biomarker for MND

There is a critical need to find a biomarker for MND to speed up diagnosis, monitor disease progression and improve clinical trials. A biomarker is a biological change that can be detected in a person to signal that they have MND, and that can be measured over time to monitor how the disease is progressing.

Previous research has suggested micro RNAs (miRNAs) present in the blood might be a biomarker for MND. miRNAs are short forms of RNA, the cell’s copy of our genetic material DNA. They are stable in the blood, can be easily measured with a blood test, and evidence suggests that they are linked to MND progression. To put it simply, if the biomarker hunt was a music festival, miRNAs would be a headlining act that a lot of people are excited about! Continue reading

Developing a blood test for MND by linking changes in the brain and spinal cord

Developing a way to rapidly diagnose and track how MND progresses over time is a ‘holy grail’ of MND research. The search for so called ‘biomarkers’ is an area that researchers funded by the MND Association are actively pursuing.

MND Association grantees Dr Andrea Malaspina and Dr Ian Pike (Blizard Institute, Queen Mary University of London) and Prof Linda Greensmith (University College London) are currently working on a project to find these biomarkers (our reference: 871-791). People with MND have been helping the researchers by regularly donating blood and spinal cord fluid samples.

QMUL-Blizad MND group

Queen Mary University of London (QMUL) Blizard Institute MND group

Continue reading

Developing the Biomarkers in Oxford Project

Biomarkers in Oxford (BioMOx) is a research project with the aim of identifying a diagnostic biomarker for MND, which could be used to track the progression of this condition.

What are biomarkers?

The aim is to identify biomarkers, or ‘biological fingerprints’ for MND. This could be through testing blood and spinal fluid (CSF) samples from people with MND, or using MRI scans and other imaging techniques to look at changes in the brain.

By understanding the very earliest changes detected in these samples at the start of MND (the biomarker), it is hoped that they could be used to work towards disease prevention and to develop more targeted therapy for those already affected by MND.

For example, including a biomarker element in future clinical trials will help us learn more about the disease and identify participants most likely to benefit from the drug being tested.

Being able to track the progression of the disease could also help with effective care-planning for people with MND. Continue reading

Endomicroscopy – lighting the way for a diagnosis

Richard Ribchester 2015At present there is no diagnostic test for MND, and diagnosis is usually determined through clinical observations and by excluding other diseases. Because of this, a definitive diagnosis of MND can take up to several months.

By developing an effective diagnostic test for MND, we will be able to diagnose MND earlier and put in place effective care and support needs sooner. Another benefit to earlier diagnosis would mean that people living with MND can be started on riluzole much earlier. Continue reading

Neurofilaments show promise as biomarker candidates for MND

TiskSaturday afternoon saw the 25th International Symposium on ALS/MND expand from two to three sessions running in parallel. Times have changed from the early years of the meeting when sessions finished at lunchtime on the second day because there wasn’t enough stuff to talk about! Rather than flitting between three different lecture halls, I opted to immerse myself in the Biomarkers session, especially since the session was being kicked off with presentations from MND Association funded investigators.  Continue reading