Networking to progress in the world of science: Mini-Symposium on MND

Conferences and symposia are a crucial part of the research world – not only for the amount of knowledge that is communicated to large audiences but also for the exchange of ideas on a more inter-personal level. Novel ideas are created there as well establishment of collaborations that might lead to new research projects and clinical trials – all in all, putting a bunch of researchers in a venue with a projector, coffee and biscuits can only lead to good things!

One of the recent events that I had the pleasure to attend was a small-scale conference – the Mini-Symposium on generic disease mechanisms in MND and other neurodegenerative disorders. Held at the Brighton and Sussex Medical School in late June, this event was a precursor to the inauguration of a new MND Care and Research Centre for Sussex, directed by Prof Nigel Leigh.

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(left to right) Prof Martin Turner, Dr Brian Dickie, Prof Dame Pam Shaw, Prof Nigel Leigh and Karen Pearce.

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Correcting the early damage seen in MND

Previous research in humans and zebrafish has shown that before symptoms arise in MND, early changes occur in the interneurones. This type of nerve cell provide a link between the upper and lower motor neurones in the brain and spinal cord.

The job of one type of interneurone (called inhibitory interneurones) is to apply the brakes on motor neurones. They work just like brakes on a bike stop the wheels from moving.

The interneurones control when chemical signals/messages (or action potentials) can be passed along the nerve cell. In MND these brakes are less effective (so to use the bike analogy, the brakes might be rusty or not connected properly).

Interneurones are being studied in more detail in a project led by Dr Jonathan McDearmid (University of Leicester), in collaboration with Dr Tennore Ramesh and Prof Dame Pamela Shaw (Sheffield Institute for Translational Neuroscience) (our reference: 835-791). Continue reading

From genes to the clinic: MND Association and ALS Association-funded researcher wins the ENCALS Young Investigator Award 2014

After attending the ENCALS meeting in May I was busy scheduling the ‘blog a day’ in June, which meant I didn’t get chance to actually report on any developments from the meeting. During our ‘blog a day’ we wrote a lot about genetics, in terms of the UK MND Whole Genome Sequencing project and the UK MND DNA bank. Therefore, I thought it would be a good opportunity to introduce a different area of genetic research and how it relates to what’s going on in the clinic.

The Award

During the European Network for a Cure of ALS (ENCALS) 2014 meeting (Leuven, Belgium 22 – 24 May 2014), Dr Ashley Jones, was awarded the Young Investigator Award.

It’s a highlight of the annual meeting, which showcases and recognises the work of the next generation of researchers in the field of MND, in this case, King’s College London-based Ashley.

But how does it feel to win such a prestigious award? Ashley said:

“Ammar phoned late Sunday evening, in a grave tone, and asked me if I was sitting down. I sat down, and began to worry. When he told me the news, I became inarticulate. I think there was some joyous laughter, and then I repeatedly asked him ‘really!?’”.

Prof Dame Pam Shaw presenting Dr Ashley Jones with the 2014 ENCALS Young Investigator Award

Prof Dame Pam Shaw presenting Dr Ashley Jones with the 2014 ENCALS Young Investigator Award

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The UK Whole Genome Sequencing project

Dr Samantha Price is the Research Information Co-ordinator at the MND Association. As well as organising the ‘blog a day’ during MND Awareness Month she also communicates the latest news about MND research. Here she blogs about the MND Association’s announcement of the UK Whole Genome Sequencing project.

It’s been a brilliant Awareness Month with blogs about zebrafish research and streaking meerkats. To end on a positive research note, we’re delighted to announce that we are funding a UK Whole Genome Sequencing project to help us understand more about the causes of MND. Utilising samples from our own UK MND DNA bank; researchers in the UK will aim to sequence 1,500 genomes to help identify more of the genetic factors involved in the disease.  Continue reading

MND Researchers: England v Italy

Tonight England will take on Italy in the FIFA World Cup. It’s fair to say England look like they have pretty poor odds of winning the World Cup (yet alone getting through the Group stages!), however I’m sure many England supporters will be cheering on their team tonight as they take on the Italians.

As we’re posting a blog a day for MND Awareness month, in light of the England v Italy game, we introduce the MND Italian researchers line-up! We may support different football teams in the World Cup, but our Italian researchers are working together with our English researchers towards a world free from MND.

The Italian MND researchers

Photo x MND

The formation of Bendotti’s team is:

Bottom, from the left: Mattia Freschi, Massimo Tortarolo, Giovanni Nardo,Nicola Secomandi, Antonio Vallarola; Top, from the left: Martina Rossi, Beatrice Bosani, Caterina Bendotti, Valentina Torti, Maria Chiara Trolese

Our research mainly focuses on studying MND mouse models with the same gene mutation, but different disease progression (see our previous blog post). Our main research objective is to identify the key molecular pathways that modulate the disease course in these mice. This will enable us to develop reliable prognostic biomarkers of the disease and treatments capable of slowing down the course of the disease.

This work is carried out in a joint international collaboration with Prof Pam Shaw (University of Sheffield, UK) and Dr Andrea Malaspina ( Queen Mary University of London, UK ).

 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.

Physical activity and MND – is there a link?

The results of new research investigating a link between physical activity and MND was presented by the University of Sheffield research group in the late-breaking news session on the last day of the 24th International Symposium on ALS/MND. Under the leadership of Prof Pam Shaw, along with Dr Chris McDermott, MND Association-funded researcher Dr Ceryl Harwood presented her findings.

Dr Brian Dickie, director of research development

Dr Brian Dickie, Director of Research Development

The background of MND and physical activity

Physical activity and the link between MND has long been debated amongst researchers.

There are a number of different types of physical activity; from leisure time (for example an evening walk) to more vigorous physical activity and athleticism (marathon runners and professional sportsmen).

Previous research back in 2008 found that Italians playing professional football had an increased risk of developing MND. However, this research is yet to be confirmed in other countries. Director of Research, Dr Brian Dickie said: “The Italian researchers also looked at professional cyclists and basketball players, but no association was found, so basically the jury has been out on whether athleticism is a risk factor for MND.”

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Same disease.. two very different mice!

The exact course, duration and rate of progression of MND often varies greatly from person to person; even when there is a known family history of the disease caused by a specific MND-causing gene (eg SOD1).

This same variability also occurs in mice. Researchers, funded by the MND Association, took two mice with the same SOD1 gene mutation from two different families (strains). By using these two mice the researchers identified a number of key changes in motor neurones that differ between fast and slow progressing forms of the disease.

Two mice… One gene

The SOD1 mouse

The SOD1 mouse model has been one of the most important MND research tools for scientists

Developing new disease models enables us to both understand the causes of MND and test potential new therapies.

Mice are commonly used in MND research and for the past 10 years or more, the SOD1 mouse model has been one of the most important research tools for scientists working in the field, particularly with testing potential new therapies.

Research published in September 2013 was carried out in a joint collaboration between Dr Caterina Bendotti (Mario Negri Institute for Pharmacological Research, Milan Italy) and Prof Pam Shaw (University of Sheffield, UK).

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New MND Association Lectureship in Translational Neuroscience

Dr Richard Mead based at the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield has been awarded the Kenneth Snowman-MND Association Lectureship in Translational Neuroscience.

Dr Richard Mead, SITraN, UK

Dr Richard Mead, SITraN, UK

The five-year Kenneth Snowman-MND Association lectureship is aimed to embed preclinical expertise in motor neurone disease (MND) models within SITraN as a national resource.

Our Director of Research Development at the Association, Dr Brian Dickie, commented: “We are delighted to be able to help secure the position of an outstanding young scientist at one of the top European centres for MND research.

“Our understanding of the causes of MND and the reasons why motor neurons degenerate is increasing rapidly and we need more researchers like Dr Mead who are ideally placed to move this new understanding from the laboratory to the clinic.”

Read more about this story on our website: New MND Association Lectureship in Translational Neuroscience.

Vive la difference!

It could be easy to assume that one motor neurone is pretty much like another, but a series of presentations on Thursday clearly showed that we need to be a little more sophisticated in our thinking.

Dr Hynek Wichterle (Columbia University) discussed how in the developing embryo, there are distinct regional subtypes of motor neurones in the spinal cord. For example, the motor neurones at the bottom of the spine can be easily distinguished from those at the top of the spine by the pattern of genes that are switched on and off – in a nutshell, different motor neurones have their own regional ‘postcode’.

Dr Wichterle went on to show that you can generate motor neurones with specific postcodes  in the lab, from embryonic stem cells . Having motor neurones  that  hopefully reflect different aspects of MND will allow researchers to better understand the subtleties of motor neurone function and develop more relevant treatment approaches.

It’s well known that some motor neurones are particularly resistant to the disease, such as the so called ‘oculomotor neurones’ that control eye movements. By looking at  the pattern of genes  being switched on and off in early mouse embryonic development, Dr Wichterle was able to induce the same pattern in mouse stem cells to create what look very much like oculomotor neurones in the dish. There is some further work to be done to check that they are indeed what he thinks they are, but they could be a very important tool in helping to understand why some motor neurones are tougher than others.

Continuing the theme, Dr Georg Haase  (Marseille) introduced an elegant way of separating different populations of motor neurones from mouse spinal cord. He focused on two subtypes of motor neurone – those that connect to the limb muscles  and those that connect to the main trunk of the body. After they are separated out, they can be grown in culture (in a dish in the lab) . He then showed that these two different subtypes of motor neurone acted very differently in their response to chemicals known as neurotrophic factors . The word neurotrophic can be literally translated as ‘nerve nourishing’ and these chemical compounds have attracted a lot of attention in the past as possible therapies for MND, with a couple being tested in large clinical trials . Unfortunately these trials have not shown any effect, but this could be because  – as Dr Haase showed in his lab studies – each neurotrophic factor only acts on a proportion of motor neurones. He suggested that the different ‘survival profiles’ he sees in his cellular studies  provide a rationale for selecting combinations of different neurotrophic factors for further testing in mice – and hopefully in man.

Prof Pam Shaw (University of Sheffield) also asked the question of what makes  oculomotor neurones  different, but her presentation took us from mouse to man. Using a technique called laser capture microdissection, which allows individual motor neurones to be removed from post mortem spinal cord tissue form MND patients, she and her colleagues are able to examine which genes  were switched on and off in the cells. Research like this requires very high quality tissue, removed shortly after death, but Sheffield happens to host one of the best MND tissue banks in the country.

She compared these ‘gene expression patterns’ in the disease-resistant oculomotor neurones with the more vulnerable motor neurones  from the lower spinal cord. There were  considerable differences in the patterns, with a much larger number of genes being switched on in the oculomotor neruones. Many of these genes could be dividied into functional families, which act on a similar biological pathway. Key protective processes activated included neurotransmission, mitochondrial function and proteasomal function – all of which are strongly implicated in MND. If human oculomotor neurones  survive by gearing up these  protective pathways, it provides possibilities that drugs can be found which act in the same way.

Our International Symposium website news stories:

International Symposium closes in Chicago

International Symposium focuses on clinical trials

International Symposium focuses on carer and family support

International Symposium begins in Chicago

Researchers unite at our International Symposium on MND

After you’ve finished reading the symposium articles that interest you, we’d be grateful if you could spare a few minutes to fill in our short online survey on our symposium reporting. Your comments really are useful and allow us to continually improve our symposium reporting. surveymonkey.com/s/alssymp 

A right Royal event

It’s 6.45 a.m. and I’m trying to find my way to the BBC Sheffield studios for a series of local radio interviews, but I’m lost in the dreaded one-way system (I knew I should’ve got the sat nav out, but it looked so easy on the map….). Just after seven I get into the studio and in front of the mike about a minute before I’m scheduled for a slot on BBC Radio Ulster. The system allows other regional stations to link directly into one of their network studios, so over the next 90 minutes I do a quick ‘tour of the country’ (Norfolk, Cambridge, Shropshire, Somerset, Teeside and, of course, Sheffield) without leaving my chair.

The reason for the early morning activity was the formal opening of the Sheffield Institute for Translational Neuroscience (SITraN) by the Queen, accompanied by the Duke of Edinburgh.  Led by SITraN Director Professor Pam Shaw, the institute offers a state-of-the-art environment for researchers working on a number of neurodegenerative diseases, with the principal focus on MND. I’d been lucky enough to have been up there last week, thrashing out the details on a new clinical biomarker study we’re going to be funding, so I’d already had the tour under more relaxed circumstances than yesterday’s occasion!

We had to get there well in advance of the royal party, but it gave me the chance to touch base with some of the scientists we’re funding, as well as catch up with representatives from other research funding bodies, such as the MRC, Parkinson’s UK and SMA Trust. The way a degenerative processes occurring in one disease will have overlap with the processes occurring in other diseases, so it’s important to catch up on what’s going on in other research fields and to discuss possible ways in which the research funding bodies might work more closely together.

We certainly knew when the guest of honour had arrived from the noise outside, courtesy of the local schoolchildren lining the main street.  The Queen and Duke of Edinburgh were taken on a tour of the new building and learned about some of the avenues of research being explored by the different specialist teams, ranging from computational biology and genetics through to development of new laboratory models and clinical research. I was keen to find out how the clinical studies we’re funding were going, so at lunch was handily sat beside the clinician who is currently running studies in airway clearance techniques and the optimum timing of gastrostomy in MND patients. He was also able to update me on his bid to the Dept of Health to conduct a trial of a new respiratory intervention known as diaphragm pacing, to which the MND Association is lending its support as a potential co-funder.

The institute will provide a fantastic working environment for researchers and I could see the energy and enthusiasm among Pam’s team that comes with moving into a ‘new home’. Ultimately, though, it’s brainpower and dedication, not bricks and mortar, that will defeat this disease. As I left, I reflected on the fact that the Association provided its first research grant to Pam Shaw almost 20 years ago, when she was first entering the world of MND research – the first of many such awards over the years. It’s good to know we backed a winner.