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.

Prof Richard Ribchester, and colleagues, at the University of Edinburgh have recently been awarded funding from the MND Association to develop a new technique that allows them to view the connections between the motor neurones and muscles, by inserting a tiny, powerful microscope. Former colleague Dr Samantha Price explains more:

Diagnosing MND

MND can be incredibly difficult to diagnose and diagnosis often includes a clinical examination, blood tests, nerve conduction tests and magnetic resonance imaging (MRI). Another investigation includes assessing the health of the motor neurones, and the connections they make with the muscle (known as the neuromuscular junction).

This is currently investigated by an electromyography (EMG) or muscle biopsy, which can be highly invasive and painful procedures.

Prof Ribchester’s Association-funded research will use an entirely different approach to assess the health of these neuromuscular junctions.

The power of an endomicroscope

Using an incredibly powerful microscope, known as a confocal endomicroscope, the researchers will place a small probe (1.5mm in diameter) onto the surface of the muscle, which will allow the researchers to make live observations at the neuromuscular junction in the clinic.


Prof Richard Ribchester and the endomicroscope (University of Edinburgh)

Prof Ribchester said: “We are very excited by the future prospects for using our ‘microendoscope’ to look at the neuromuscular junctions inside a patient’s muscles. This will allow us to observe how the disease may be progressing or, more importantly, to assess the effect of novel and experimental treatments on the neuromuscular junctions in MND.

“In order to view the neuromuscular junctions properly, we need highly specific fluorescent dyes that will stick to the nerve endings and make them glow. This will enable us to ‘see’ the neuromuscular junctions clearly by the optical fibres in our microendoscope.” 

By using fluorescent ‘glowing’ dyes, which bind to the nerve endings, this will enable the researchers to view the neuromuscular junction bright and clear. However, identifying these specific dyes will be the main focus of the project.

Prof Ribchester said: “We have already shown that our microendoscope works well in mice genetically-engineered to express a fluorescent protein on their nerve endings; however humans do not express this fluorescent protein so we will need to create a safe injectable dye in order to view the neuromuscular junctions in humans using our microendoscope.

“Therefore the most important step in this project will be using sophisticated molecular biology techniques to discover fluorescent dyes that can be used with our microendoscope, before testing them on human muscle tissue. This will enable us to identify the best dyes for viewing living neuromuscular junctions in patients.”

The importance of this research

Already tested in mice, the researchers aim to further develop microscopic clinical imaging by creating a fluorescent dye that can be used with the microendoscope in humans.

Ultimately, this technique will not only allow us to view live neuromuscular junctions in people, but it will be a step closer towards a diagnostic test in the clinic to enable earlier diagnosis and monitoring of new treatments.

More information:

You can read more about this research project funded by the Association on our website and also in our ‘Research we fund’ information sheet.

Dr Emma Hodson-Tole’s MND Association-funded research at Manchester Metropolitan University (MMU) is investigating a pain-free diagnostic test for MND using ultra-sound technology – you can click here to view a video of Dr Hodson-Tole explaining her research.

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

A taste of Brussels…

Brussels 2014On 4 November, we welcomed two of our funded researchers to our offices in Northampton. Ruxandra Mutihac and Matt Gabel gave us a ‘taste’ of what’s to come for this year’s 25th International Symposium on ALS/MND, by speaking to us about their research.

The symposium is the World’s largest MND-specific research conference and is now only two weeks away! Continue reading

Very ‘ice’ research

The ALS #icebucketchallenge, which started in America, has now well and truly hit the UK! The social media craze has seen thousands of people getting involved in raising awareness of ‘ALS’( the most common form of MND), and funds for the Association, by placing a bucket of ice-cold water over their heads. But what happens to the donations?

The #icebucketchallenge has raised awareness of MND and has got people asking ‘what is ALS/MND?’ The donations raised will enable us to support people with MND and fund vital research. We thought we would share with you some of our ‘coolest’ research this bank holiday weekend, which the #icebucketchallenge is helping to fund:

The UK MND DNA bank (link to previous blog) freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)

The UK MND DNA bank freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)

Continue reading

Postcard from Australia

Emma Devenney at this year's symposium in Milan

Emma Devenney at last year’s symposium in Milan

Dr Emma Devenney is an MND Association and Neuroscience Research Australia funded PhD student investigating the Cerebellum in MND and Frontotemporal Dementia at Neuroscience Research Australia. She is finding out what role it plays in the symptoms of patients with the C9orf72 mutation. Here she blogs about her work from Australia!

Finally after more than 12 months of preparation and anticipation I touched down in Sydney to be greeted by a city in the throes of early summer. Sydney in the summer is the epitome of the Australian dream and it is easy to see how it has enticed many Irish and British immigrants to its shores. The blue skies, beautiful beaches and a lively cultural and social scene are amongst many of the cities attractions and distractions.

Neuroscience Research Australia is in the exuberant Eastern suburbs of Sydney; an area where the British and Irish expatriate communities have integrated well into Australian society and are as reliant on a daily ‘flat white’ as any self-respecting Australian. The research centre is located down the hill from the Prince of Wales hospital in the suburb of Randwick. Continue reading

The ALS biomarkers study: a journey into the disease

Dr Andrea Malaspina is an Association-funded researcher investigating biomarkers, or ‘biological fingerprints’ of MND. Here he blogs about working with patients and basic science.

I regularly meet people living with MND due to my role as a Consultant Neurologist at the Bart’s and the London MND Care Centre and one of the most common questions I get asked is about getting involved in research. My research enables people living with MND to take part, therefore bridging the gap between the lab and the clinic.

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

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

Continue reading

MND Diagnosis: The utility of standard frame rate b-mode ultrasound imaging

Kate Bibbings is a PhD student funded by the MND Association, who is using ultrasound as a diagnostic tool for MND. Like Dr Martin Turner, she is hoping to speed up the diagnosis of MND. Based at Manchester Metropolitan University, here she gives us an introduction to her research.

B Mode ultrasound has been used a number of times to successfully identify muscle twitches. Recordings may be made of activity and movement within the selected muscle and analysed in order to determine the presence of muscle twitches. This has previously been done by individuals with experience in ultrasound video analysis and using the technique of manual identification/ classification. However, this is a subjective and time consuming technique.

My research

The aim of this study is to evaluate the performance of previously developed automated ultrasound analysis techniques, whilst investigating improvements or alternatives that may be used for the automated detection of muscle twitches. This will be done with the scope to making a diagnosis of Motor Neurone Disease whilst blinded to the actual clinical diagnosis, using only ultrasound images and the automated twitch detection technique. This will enable the viability of using ultrasound as a clinical diagnostic technique to be assessed and compared to the current technique of intramuscular Electromyography.

Currently, work is being carried out into investigating the effects of probe orientation and positioning on image quality (determined by such features as fascicle definition). It is hoped that this work will pay dividends when we begin collecting our first pilot data at Royal Preston Hospital, late July 2014.

KAte bibbings

The Muscle Function Lab at Manchester Metropolitan University

Thank you for reading our ‘blog a day’ this Awareness Month. We would gratefully appreciate your thoughts and feedback via this short 2 minute survey.

Developments in BioMOx

Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Senior Clinical Research fellow, Dr Martin Turner writes about recent developments in his BioMox study.

Dr Martin Turner, MRC/MND Association Lady Edith Wolfson Clinical Research Fellow

Dr Martin Turner, MRC/MND Association Lady Edith Wolfson Clinical Research Fellow

My first ever blog. I decided to share developments in ‘BioMOx’ – the Oxford Study for Biomarkers in MND, which has been funded through the MND Association’s pioneering Lady Edith Wolfson Fellowship scheme (in conjunction with the Medical Research Council).

About BioMOx

Between 2009 and 2013, over 70 people living with MND (and some healthy people of similar age for comparison), took part in a new type of patient-based study. Men and women of all ages (from 28 to 86), some with primary lateral sclerosis (PLS) as well as a range of the more common amyotrophic lateral sclerosis (ALS) types, all gave up their time to attend for a day or two of tests in Oxford. Continue reading

Taking part in BioMOx..

To end volunteer week, Katy Styles, who is a Campaigns contact for the East Kent Development Group of the MND Association, blogs about her and her husband Mark’s experience of volunteering to take part in the Biomarker’s in Oxford (BioMOx) study.

It started as an innocuous question following a neurology appointment at the Oxford MND Care Centre, Mark and I asked “Now what can we do for you?”

Following a phone call and some form filling, Mark and I had volunteered to take part in Dr Martin Turner’s BioMOx Project. Mark as a person with MND and me as a control of the same age.

We didn’t know what to expect as we were scheduled to take part in two days worth of tests, which included two scans and a written test. In between time in the scanners however, we were able to enjoy everything Oxford has on offer. Continue reading

A healthy control – Dr Scott Allen

Dr Scott Allen is a Senior Post Doctoral Researcher at the Sheffield Institute for Translational Neuroscience (SITraN). Here he blogs about his experience as a research volunteer in an MRI scanner.

Today, as part of on-going work by Doctor Tom Jenkins and Prof Pamela Shaw at the Sheffield Institute for Translational Neuroscience (SITraN), I volunteered as a healthy control to have a full body MRI scan.

Mitochondria and MRI

Tom’s work is very similar to my own; he aims to determine whether there are differences in the way that people with motor system disorders produce energy compared with healthy volunteers. Mitochondria are known as the “powerhouses” of human cells and produce energy. Tom wants to find out whether there is evidence for abnormal function of these mitochondria by doing magnetic resonance imaging (MRI) scans of the brain. Continue reading