New genetic discoveries tell us more about what causes MND – Part 1

Today some exciting news about the genetics of MND was published in the scientific journal Nature Genetics. The results come in two research papers published in the same issue of the journal.

This blog post discusses the results of the first of these papers for which King’s College London based Professor Ammar Al-Chalabi was one of the leading researchers. A post on the second paper will follow later.

Here we’ve given an overview of what the researchers have found, what it means for people with MND and how the analysis was conducted. You can read a more detailed explanation of the research results from the King’s press release. Continue reading

Professor Ammar Al-Chalabi wins prestigious prize

Huge congratulations to Professor Ammar Al-Chalabi for winning the prestigious Sheila Essey Award at the American Academy of Neurology (AAN) research conference taking place in Vancouver, Canada.

Professor Al-Chalabi is an MND Association funded researcher and Professor of Neurology and Complex Disease Genetics at King’s College London. He is also the Director of our MND Care and Research Centre at King’s.

The Sheila Essey Award is jointly given by the AAN and the ALS Association in the USA, and recognises an individual who has made significant research contributions in the search for the cause, prevention of, and cure for amyotrophic lateral sclerosis (ALS, a type of MND).

Prof Al-Chalabi is receiving the award for his role in helping us learn more about the complex causes of MND, including the role of genetics in the non-familial form of MND.

“It is a wonderful acknowledgement of the work the present and past members of my team have done in ALS/MND research,” Prof Al-Chalabi said. Continue reading

Palliative Care Research – new funding available

Today an exciting announcement was made about three organisations working together to increase our knowledge on the best way to provide palliative and end of life care. The MND Association and the Chief Scientists Office in Scotland (CSO) will be working with Marie Curie on a new research call.

Marie Curie Logo

In addition to a £1million funding pot from Marie Curie, the CSO will contribute £225,000 of funding and MND Association will contribute up to £200,000. Scientists, clinicians or healthcare workers are invited to submit their outline applications by 14 January 2016.

Acting on what you told us

The areas that we’d like to fund are based on a project that was completed in January 2015, known as the ‘Palliative and End of Life Care Priority Setting Partnership’, shortened to ‘PeolcPSP’. At the core of this 18 month project were responses to an online survey, where many people shared their questions or experiences about the end of life. We were pleased that many people affected by MND took part.

From those survey responses, we worked out that there were a massive 83 topics that would be suitable for a research study (and where no conclusive studies had already been conducted). All of these are important topics to investigate, so we’re hoping that researchers with an interest in working in any of these topics will think about submitting an application for funding.Palliative-care-2

So what kind of topics are included?

The topics for the call are the list of 83 questions from this earlier palliative care research study (the PeolcPSP study mentioned above). It is too long a list to include in this post, but the overarching themes include how (best to):

  • communicate topics on palliative and end of life care
  • manage symptoms and medications
  • provide support for carers and families
  • provide support in bereavement
  • provide support for staff (and staff training)
  • co-ordinate care services
  • provide access to services
  • decide where the care should be and what type of care

Where can I find out more?

A press release and more information on how to apply for this funding is available on the Marie Curie website.

The Palliative and end of life care Priority Setting Partnership final report is available online. There’s also a video about the project explaining how it happened and why it is important.

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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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”.

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Tilting the scales

We know that in the 5-10% of cases where there is a strong family history of MND, there is likely to be a genetic cause at work, acting like a weight to push the scales in favour of the disease occurring.  These gene mutations are hidden somewhere within the 15 billion or so letters of DNA that make up our genome and, through collecting samples from extended families affected by the disease, coupled with huge advances in gene-hunting technology, researchers have managed to identify over two-thirds of the causes of hereditary MND in recent years and are hot on the heels of the other causes.

scales

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Clusters of MND – What can we learn?

When you hear the word ‘cluster’ the first thing that comes to mind is probably a group of stars – not MND. During a plenary talk by Dr Ettore Beghi on Saturday 7 December the question was:  ‘Is there anything we can learn from clusters in MND?’

What do we mean by clusters? 

Dr Beghi began his talk by defining a cluster as “a health related event with temporal or geographical activity.” Meaning: a number of people  are diagnosed with a disease in either a specific time period or area. He also highlighted that if rare diseases are found in clusters then this may require environmental factors to be investigated.

We already know that MND is thought to be caused by a combination of subtle genetics, environmental and lifestyle factors. At the MND Association we regularly receive enquiries about apparent ‘clusters of MND’ and I was looking forward to hearing Dr Beghi’s talk on the subject.

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Unravelling TDP43 toxicity

Background to TDP43

A characteristic sign of motor neurones affected by motor neurone disease is the clumps of protein visible down a microscope. Although these proteins have been observed in motor neurones from people affected by MND since the earliest descriptions in the 1870s, a key discovery was made when the identity of a protein, common to all types of MND, was unveiled as ‘TDP43’ in 2008.

Two years later a second protein called FUS was also been found to be common to all types of MND. More information on this aspect of MND can be found in an article on our research blog.

One of the exciting things about these two discoveries was that they were both linked to a set of biological pathways, known as RNA processing. The was the first major clue that RNA processing was involved in MND. When the discovery of genetic defect in the C9orf72 gene came along in 2011, that made a third MND-causing gene defect that linked to RNA processing.

The first session of the 24th International Symposium on ALS/MND after lunch yesterday was dedicated to the topic of RNA processing and dysregulation. Several of the talks presented work on understanding the role of TDP43 in 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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A view from the President

After we posted yesterday’s blog (Thursday 10 October) about Giovanna Mallucci’s research in Leicester, we received a report on the story from the President of the MND Association, Prof Colin Blakemore.

The researchers identified a key pathway that might be a turning point in the search for effective treatments for many types of neurodegenerative disease and we couldn’t resist posting Prof Blakemore’s views:

The team at the MRC Toxicology Unit in Leicester has been studying mice with a so-called prion disease (very similar to Mad Cow Disease), produced by genetic modification of the mice or by infection. Prion disorders are known to be caused by unusual “misfolded” protein molecules accumulating inside nerve cells, and last year Professor Mallucci discovered why the nerve cells die. When unusual protein molecules build up inside a nerve cell, the cell shuts down the production of its own proteins in self-defence. But if the shut-down continues for too long, the nerve cell starves itself of its own proteins and dies.

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