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. Read the rest of this entry »

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

Read the rest of this entry »

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. Read the rest of this entry »

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. Read the rest of this entry »

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. Read the rest of this entry »

Neuroimaging – can we see more clearly?

Plenary speaker Dr Massimo Filippi put this question to delegates on the second day of the 24th International Symposium on ALS/MND.

Opening the session on neuroimaging, Dr Filippi gave an excellent review on what we currently know about this area of research, and ultimately answering whether or not we can see more clearly in MND?

Neuroimaging - now and then.

Neuroimaging – now and then.

It’s all in your head – Magnetic Resonance Imaging (MRI)

Over the past ten years there have been significant advances in the identification of neuroimaging patterns in MND. Dr Filippi focused mainly on the use of MRI neuroimaging (a technique used to visualise changes in the brain). He stated: “Through the use of MRI we have been able to detect cortical thickness of the Cerebral cortex (the outermost layer of the brain), which is significantly reduced in MND”.

Read the rest of this entry »

Progress in the MND Oxford BioMOx project

MND Association funded researcher Dr Martin Turner at University of Oxford has identified a pattern of degeneration in the brains of people with MND that is linked to the level of disability.

This finding brings us closer to identifying a biomarker that can be used to speed up the diagnosis of MND, which can be delayed on average by a year since first symptoms.

This is the third finding to be announced since Dr Turner was awarded with the MRC/MND Association’s Lady Edith Wolfson Clinical Research Fellowship in 2008.

You can read more about this exciting finding on our website:

Progress in the Oxford BioMOx project | 2013 | MND Association.

Reference: Stagg CJ, Knight S, Talbot K, Jenkinson M, Maudsley AA, Turner MR, Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS. Neurology 2013; DOI 10.1212/WNL.0b013e318281ccec

Why we need biomarkers

Yesterday’s announcement by the biotechnology company Trophos SA of the lack of effectiveness of their compound olesoxime adds to the long list of drugs that have failed to live up to their early promise in the lab.

It’s a story that’s common across the world of neurodegenerative disease, including common conditions such as Parkinson’s disease and Alzheimer’s disease. The path from bench to bedside is fraught with pitfalls….

In their press release, Trophos suggested that trials have to be conducted when the ‘window of opportunity’ is greatest – the sooner a drug is administered the better its effect is likely to be. Otherwise, we don’t know whether these treatments genuinely do not work or is it simply a case of ‘too little, too late’?

Certainly, companies such as Biogen Idec have picked up on this, restricting the time limit for inclusion in their trial of dexpramipexole to two years from symptom onset, as opposed to the three year (and sometime longer) limit that has been used in previous trials. It means that Biogen Idec has to involve more local MND clinics to recruit the numbers needed, for the trial, which increases the cost, but they view this as necessary if they are to increase the chances of a positive result.

Similarly, the way MND manifests and progresses can be so different in one individual compared to the next, meaning that trials need to recruit large numbers of participants to reduce the statistical ‘noise’ – once again increasing the already high cost and complexity of the trial.

We will only make major inroads into earlier diagnosis and more accurate predictions of how the disease will progress if we can identify biomarkers – specific biochemical and/or structural changes that occur within the brain and spinal cord that provide us with a unique ‘fingerprint’ of MND. 

Biomarkers can also be tailored to look at the effects of specific drugs in trials. Even if it is unclear whether a drug is working on the ‘outside’ (on muscle function for example) it would at least be possible to confirm it was working on the ‘inside’ by reaching the right parts of the brain and spine and acting on the correct chemical processes.

In a nutshell, biomarkers would likely lead to smaller, faster and more accurate trials. That would mean trials could be performed more cheaply – and cheaper trials would almost certainly mean more trials.

This is why the MND Association sees biomarker research as so important. We are currently supporting three clinical biomarker projects (in London, Oxford and Sheffield) which are among the most comprehensive examples of this research in the world. Without the commitment and enthusiasm of those who participate, we wouldn’t be able to create these vital research resources which, as highlighted in previous postings, are beginning to generate promising early results.

But these projects are just the start. Their findings will need to be confirmed in much larger studies, involving the collaboration of MND clinics across many countries, collecting clinical data and samples to precise scientific protocols. This was the rationale behind a major biomarker funding initiative announced earlier this year under the European Union Joint Programme in Neurodegenerative Diseases (JPND). Established by 23 European countries, the JPND Research Call invited funding bids to assist the harmonisation of biomarker collections and the development of new methods of analysing the samples.

On Friday, JPND announced the four projects shortlisted on the basis of “scientific excellence” for a share of the €15 million (approx £12.6 million) research fund. One of these projects is SOPHIA (Sampling and biomarker OPtimisation and Harmonisation In ALS).

Co-ordinated by Prof Leonard van den Berg, the SOPHIA initiative will span up to 16 centres across 12 European countries, including the MND Association’s Sheffield and Oxford Care Centres. The precise level of funding has not yet been determined, but nonetheless this provides a fantastic platform on which major international biomarker research can be developed. We will of course keep you posted once the final outcome is known.

Promising news for keeping the motor neurone neighbourhood safe

There was standing room only in the first of the dedicated scientific sessions of the Symposium last week. All had gathered to hear Prof Stan Appel inform them of the latest chapter of this story on the role of inflammation in MND.

Listening to his presentation I got the gist of the overall positive message – a real step forward in MND research – but to report in any more detail of how and why was a step too far for my brain when I was in Sydney! Reading through my notes when I got back to the office, I was determined to get to the bottom of this science. It helped me to write a non-technical summary of it as I went. It’s perhaps a bit more technical than our normal blog posts – but I couldn’t resist the opportunity to (try and) share my new found knowledge. So here goes:

Inflammation is one response of the immune system. The immune system is a community of cells that exist within your body to protect it from damage and to maintain its status quo. Given its important function, it is perhaps reassuring to know that how it works is mind-blowingly complex!

In the brain and spinal cord, a slightly different defence system exists in comparison to the rest of the body. It is now common knowledge that motor neurones are surrounded by cells that support their function – known as glial cells. Within the community of these glial cells there are ‘police’ cells called microglia. Prof Appel’s lab has contributed many elegant studies to a consensus of research showing that in MND these police cells operate a delicate balance between protecting the environment around motor neurones and triggering a toxic atmosphere. Gradually the toxic atmosphere prevails.

In Sydney, Prof Appel discussed another component of this defence system, ‘regulator T-cells’. Continuing the police analogy, T-cells patrol the blood, rather than the brain and spinal cord tissue of microglia. As their name suggests, regulator T cells regulate the response rate of removing toxins and maintaining a healthy environment, in particular they regulate microglia by sending out specific chemical signals.

Prof Appel wanted to know how the interaction of T-cells with microglia is affected in MND. He found that a large ‘police presence’ (or high numbers) of regulator T-cells influence microglia to maintain their protection of motor neurones. In other words, large numbers of regulator T-cells kept motor neurone death at low level, showing itself as a slower phase of disease progression. As the levels of regulator T-cells get lower, the microglia turn toxic and the rate of progression of the disease speeds up. These conclusions were based on studies in mice models of MND and in patients at different stages of MND – by analysing blood samples for the presence of regulator T-cells and comparing this with what they knew of their symptoms.

This information presents two opportunities to MND researchers – firstly if therapies can be developed to maintain the levels of these regulator T-cells they may slow down the disease; and in the meantime, chemical markers in the blood, used in these studies, may be a valuable biomarker to measure the rate of progression.

Follow

Get every new post delivered to your Inbox.

Join 2,112 other followers