More information for families affected by inherited MND available online

In April this year MND clinician-researchers Professors Martin Turner and Kevin Talbot at the University of Oxford organised an information day about the rare, inherited form of MND called ‘Families for the Treatment of Hereditary MND’ (FATHoM). The day was filmed and podcasts of the talks have recently become available. This article gives an overview of each talk and a link to the video. 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

Using DNA Bank samples to create iPSC models of MND

Induced pluripotent stem cell (iPSC) technology has enabled researchers to create and study living human motor neurones in the lab, derived originally from patient skin cells.

DNABankLogoThis project (our reference 80-970-797) is a collaboration between the labs of Professors Chris Shaw and Jack Price at King’s College in London and Siddharthan Chandran in Edinburgh. It aims to use the already collected white blood cell samples within the UK MND DNA Bank to create a larger number of new iPSC models of MND. Ultimately creating an MND iPSC cell bank, these models will enable researchers to better understand the disease and screen potential new drugs. Continue reading

“To test or not to test”, that is the question

A huge ‘atlas’ mapping the locations of motor neurone disease (MND) causing mutations within the genetic code has been collated. This has followed years of genetic analysis and sequencing of the DNA of people with MND, and their family members.

The people who have given their time and DNA have played a hugely important part in helping researchers learn more about MND, particularly the inherited form of the disease. Dr Benatar, who spoke in this session highlighted “there is a desire and interest by people who may have inherited MND to contribute to research into this disease, if not for their benefit then for the benefit to future generations of their family“.

The first session on day two of the Symposium looked at the topic of genetic testing and counselling. All the presentations had a common theme of this topic being a two-way street – after all the help people with MND and their families have given to help with research, now research efforts have been focussing on the ways to better help those who decide to have genetic testing for inherited/familial MND. Continue reading

New inherited MND-causing gene identified – TUBA4A

An international team of researchers, led by MND Association-funded researchers based at King’s College London, have identified mistakes in the TUBA4A gene as a new cause of the rare inherited form of MND.

This new MND-causing gene causes the cell’s structure, or skeleton, to break down – resulting in the cell being unable to transport molecules from one end of the cell to the other.

TUBA4A falls off the track

The TUBA4A gene is responsible for the Tubulin, alpha 4A protein and the researchers have found that the genetic mistake in the TUBA4A gene causes the microtubule network to breakdown in MND.

The microtubule network is a bit like a railway system. Normally, the healthy TUBA4A protein acts like a train, allowing the cell to transport molecules along this railway track to where they’re needed. As well as transporting molecules around the cell, the microtubule also acts as a skeleton within it (known as the ‘cytoskeleton’). Continue reading

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

Clinical trials in a dish?

A packed room at the 24th International Symposium on ALS/MND was given a fascinating whistle stop tour covering stem cells, robots and cellular garbage clearing, by Dr Steve Finkbeiner of the University of California, as well as a glimpse into the future of developing ‘disease in a dish’ models of MND.

Dr Finkbeiner outlined how his lab is attempting to conduct “clinical trials in a dish” by generating huge numbers of cultured neurons cells for automated ‘high throughput analysis’ of their health and death. As he says, “we’re basically trying to develop a comprehensive physical examination for nerve cells”. Continue reading

Degenerating Brains

“One in six of over-80 year olds will get a neurodegenerative disease. We’ve got to find ways to slow, stop or reverse these conditions” was the distinctly political message at the opening of this public symposia on “Degenerating Brains: new research into Alzheimer’s, Parkinson’s and Motor Neurone Disease”, run jointly by the Wellcome Trust and the Medical Research Council. The evening began with the world premiere of a short film explaining the importance of continuing to pursue research into these conditions (coming soon to an internet near you.. !).

The lectures started by Prof John Hardy’s excellent overview of genetics, illustrated by advances in Alzheimer’s Disease. “It’s the golden age for being a geneticist” he commented. I particularly enjoyed his explanation of the much quoted research paper by Manolio et al 2009 (Its Figure 1 in this OPEN ACCESS (yeah!) paper –if you really want to look at it!). “There are now recipes for finding causes of diseases that fall anywhere on this graph” Prof Hardy explained. Whether they are rare genetic mistakes that have a big impact (make a big contribution) on whether someone develops a condition) or more common genetic mistakes that have a smaller overall contribution. His closing comment “Geneticists are finding the jigsaw pieces to give to the cell biologist and neuropathologists to put together”, was a theme that the next speaker, Prof Chris Shaw, continued.

Prof Shaw, MND Association grantee, eminent scientist and clinician based at King’s College London, began his talk by laying down a challenge to the younger generation of scientists in the audience “I’m banking on you to find the answers to my degenerating brain”. He went on to explain how the discovery of genetic mistakes in SOD1, TDP-43 and FUS has led us to a greater understanding of the biological pathways involved in motor neurone degeneration in MND. Prof Shaw’s research has led him to develop close relationships with families affected by the rare, inherited form of MND and he ended his talk with a thank you to them for their help.

The concluding presentation was given by Prof David Rubenstein from Cambridge University, describing how advances in understanding Huntingdon’s disease research will act as a model for driving advances in other neurodegenerative diseases.
The consortia of funded researchers have got together to create a blog site for posts about Alzheimer’s Disease, Motor Neurone Disease or Parkinson’s Disease, why not add this link to your favourites too (and if you’re a twitter fan, you can follow them @dneurons )

Brain Awareness week

Every March, Brain Awareness Week (11 – 17 March 2013) unites people of all ages worldwide to raise awareness of brain research. There are 45 free events across the UK, including seminars and school visits.

On the evening of the 11 March Belinda attended the free award ceremony for the winner of the Europe PubMed Central-led science writing competition ‘Access to understanding’, which included a large number of entries on an MND paper.

On the 13 March University College London (UCL) will be running a free public symposia on ‘Degenerating Brains’. As well as talks on Alzheimer’s and Parkinson’s disease, Prof Chris Shaw (King’s College London) will be speaking about MND. Due to the popularity of this event it is now fully booked.

Our Brain Research

Dr Martin Turner
Dr Martin Turner

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

Continuing and expanding  BioMOx Dr Martin Turner has also been awarded his second MRC/MND Association Lady Edith Wolfson Clinical Research Fellowship to carry on his BioMOx project which is to begin in August 2013.

Dr Turner will be broadening the BioMOx project to include people identified as being at risk of developing MND from families with a history of the disease but who are not yet showing symptoms.

Dr Ramesh Tennore

Dr Ramesh Tennore

Dr Tennore Ramesh’s interneuron findings A recent study by Association funded researcher Dr Tennore Ramesh from the Sheffield Institute for Translational Neuroscience (SITraN) has shown that even before the symptoms of MND occur, at the earliest stages of the disease, ‘connector neurones’ known as interneurons are already becoming damaged in the zebrafish.

Prof Mara Cercignani’s MRI scans project Starting in October 2013 Prof Mara Cercignan’s Association funded PhD studentship will use brain magnetic resonance imaging (MRI) scans that have already been obtained from many studies at King’s College London over the past 16 years.

This project will apply new ideas in medical computing to old data in order to identify how MRI changes in the brains of people with MND evolve. This will then enable the development of a new method to ‘stage’ MND progression so that brain abnormalities can be detected earlier.

Tissue Donation and MND

Tissue donation is a generous gift that can make a vital contribution towards MND research. Researchers investigating MND are particularly interested in the whole of the brain and spinal cord tissue, otherwise known as the central nervous system (CNS).

A brain and spinal cord tissue donation is made from either a healthy individual or somebody with MND after their death. To find out more information about tissue donation please see our information sheet on our website.

Raise Awareness of MND

I Am Breathing

I Am Breathing

Our 2013 Awareness Month campaign is focussed around a film called I Am Breathing. The hard-hitting documentary tells the story of Neil Platt, who was diagnosed with MND just after his son, Oscar, was born.

Neil wanted to leave a legacy for Oscar and also raise awareness of MND. We hope that thousands of people will see the film on or after a special Global Screening Day, Friday 21 June, Global MND Awareness Day.The Association has joined forces with the film makers, the Scottish Documentary Institute, and with Neil’s family to make sure this powerful story is shared as widely as possible when the film is released during the Awareness Month in June 2013.

You can help fulfil Neil’s goal of raising awareness by hosting your own screening of I Am Breathing on 21 June 2013 – MND Global Awareness Day.

MND stem cell study identifies TDP-43 astrocytes as not toxic to motor neurones

Funded by the MND Association, international researchers have used stem cell technology to learn more about the relationship between motor neurones and their support cells.

These findings highlight the potential of stem cell technology as a tool to create new human ‘in a dish’ cellular models of disease to learn more about the causes of MND.

Prof Siddharthan Chandran and Sir Prof Ian Wilmut at University of Edinburgh looking at a stem cell image

The research group included MND Association funded researchers Prof Siddharthan Chandran and Sir Prof Ian Wilmut from University of Edinburgh, Prof Chris Shaw from King’s College London and Prof Tom Maniatis from Columbia University in America.

This important finding was published in the scientific journal PNAS on 11 February 2013. This new finding follows on from previous work published by this research group in 2012 where they demonstrated the proof of principle of creating human motor neurones with MND in a dish.

Why we need an astrocyte model of MND

Astrocytes, so called because of their star-like appearance, normally act as neurone support cells to nourish and protect motor neurones. They act with motor neurones to ensure that they can continue to function.

From previous studies, we know that when these cells begin to dysfunction, they can become toxic to motor neurones to contribute to MND. Finding out why astrocytes can cause motor neurones to degenerate is an issue of ongoing debate – we recently gave an update on this from the International Symposium.

Being able to grow human astrocytes in a laboratory dish is of importance to be able to learn more about the relationship between astrocytes and motor neurones in MND.

Creating human astrocytes in a dish

Using cutting-edge stem cell technology, the research group reprogrammed skin cells into astrocytes in a laboratory dish. The skin cells were donated by people with MND who have a family history of the disease caused by known mistakes in a gene called TDP-43.

Led by Prof Chandran and colleagues, the research group aimed to identify whether these cells would develop the ‘hallmarks’ of MND in a laboratory dish.

By studying the characteristics of these human astrocytes with faults in the TDP-43 gene, the research group identified that they shared the same qualities as cells affected by MND. The astrocytes had increased levels of TDP-43 found in areas where it isn’t usually found – outside of the control centre of the cell. They also found that the astrocytes didn’t survive as long as astrocytes created from skin cells of people that didn’t have MND.

This means that the human astrocytes created by Prof Chandran and colleagues using stem cell technology develop MND-like characteristics. This new model can be used to study how motor neurones develop the disease in a system that is directly relevant to people living with MND.

Answering whether faulty astrocytes affect healthy motor neurones

The next question that this research group wanted to answer was whether these faulty astrocytes had an effect on healthy motor neurones.

By growing faulty TDP-43 astrocytes with healthy motor neurones, the research group identified that the survival of motor neurones was not adversely affected.

This was surprising as other research groups have shown that when astrocytes have faults in the SOD1 gene (which cause one in five cases of MND with a family history) that motor neurones are compromised, even if the motor neurones were originally healthy.

TDP-43 is found within tangled lumps in over 90% of cases of MND (irrespective of whether it was caused by an inherited genetic mistake). However, when MND is caused by SOD1, TDP-43 is not found in these tangled lumps. This important difference could be leading to the key difference in whether astrocytes become toxic to contribute to causing MND.

These findings will of course need to be verified by an independent research group to determine that they are valid, but the results suggests that SOD1 and TDP-43 could be causing havoc in motor neurones in slightly different ways, both avenues leading to MND.

Our Director of Research Development, Dr Brian Dickie comments: “From a therapeutic perspective this is important because it means that specific treatments targeted at astrocytes may only be relevant and effective, in specific subsets of patients who will have to be carefully selected for drug trials.”


Our news release on this finding.

March 2012 finding: Association-funded stem cell study achieves milestone

Serio A et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. PNAS 2013