The not so powerful omega-3

Omega-3 fatty acids have been in the media a great deal over recent years. They can lower our risk of heart disease and they may even have neuroprotective properties (for example limit damage to the brain and spinal cord after acute injuries).

But, what about in MND? Could this dietary supplement have an effect?

MND Association-funded researchers have found out, rather unexpectedly, that the omega-3 fatty acid eicosapentaenoic acid (EPA) actually accelerates disease progression in an animal model of MND which is based on a SOD1 mutation, when EPA is given before symptoms first appear (this is sometimes known as the pre-symptomatic stage).

Why omega-3 might have had an effect

Omega-3 polyunsaturated fatty acids are natural compounds primarily found in oily fish such as sardines, mackerel or salmon. They have been widely associated with significant health benefits and researchers have reported that some long-chain polyunsaturated fatty acids may be beneficial in several neurological conditions.


Previous research in rats has shown that dietary food supplements, containing omega-3 long-chain polyunsaturated fatty acids (including EPA), reversed age-related problems in neurones (nerve cells) and also enabled the growth of new neurons.

The neuroprotective properties of EPA could occur through a variety of mechanisms such as reducing oxidative stress (damage due to low oxygen levels), reducing neuroinflammation  and the activation of anti-‘cell death’ pathways. These are all factors that are relevant in MND.

A number of studies have found that high blood lipids (the breakdown product of dietary fats) are a common feature in ALS (the commonest form of MND), and are correlated with increased survival. High-fat diets have been studied in the lab to further investigate this and have been shown in mice to delay motor neurone death and extend lifespan.

What the researchers found

Due to these previous studies the researchers decided to study one omega-3 long-chain polyunsaturated fatty acid in particular, EPA, to assess whether it had neuroprotective effects in a mouse model of ALS based on a mutation in the enzyme SOD1.

Mouse models are commonly used to study the causes of the disease and investigate potential treatments in MND. A SOD1 mouse model is a mouse that has been given a faulty MND-causing gene producing an enzyme known as ‘SOD1’, which is known to cause 20% of cases of the rare inherited form of MND.

The researchers intended to study the effects of dietary EPA when given at disease onset (the symptomatic stage when symptoms first appear) or at the pre-symptomatic stage.

The mice were fed either a standard rodent powdered diet (control) or a diet supplemented with EPA-enriched oil. The researchers then looked at a number of factors such as: disease progression, survival and body weight to find out if there were any differences.


When a diet supplemented with EPA was given at the symptomatic stage there was no significant difference in the development of MND compared to the control group (mice who were fed a standard rodent powdered diet). However, rather unexpectedly, when the EPA diet was given at the pre-symptomatic stage, the researchers found that the diet accelerated the progression of MND, but did not affect disease onset.

Glial cells (such as astrocytes and microglia) were also affected, and found in reduced levels when the mice were given the EPA diet.

Overall, the researchers found that long-chain omega-3 fatty acid EPA-enriched diets have no impact on disease onset or survival. Unexpectedly, if dietary EPA is given before symptoms appear it can actually accelerate the progression of MND.

What this means for people living with MND

The omega-3 fatty acid EPA, although it may have other health benefits, appears to have the potential to be more damaging rather than protective in this specific MND mouse model. The results from this study have highlighted the need for caution by those who are at risk of developing MND, who may use these long-chain omega-3 fatty acids dietary supplements, which are freely available, over prolonged periods of time.

This study has shown that individuals who carry the SOD1 inherited form of MND in particular should take extreme caution with diets enriched in long-chain omega-3 fatty acids such as EPA. For the future, it remains to be seen if EPA has also negative effects in other models of MND (eg zebrafish or flies with the C9orf72 mutation).

Dr Adina Michael-Titus (Blizzard Institute, Queen Mary University of London), one of the researchers involved in the study, commented “The most important point, in my view, is to be aware that we do not have yet the scientific evidence to prove that EPA or any other omega-3 fatty acids are dangerous for all forms of MND. The only experimental evidence we have so far is for a particular SOD1 mutation which leads to this disease (where the faulty SOD1 mutation is greatly overexpressed). More work is required and future research will help us fully assess and understand the potential or the risk associated with omega-3 fatty acids in people living with MND.”

Dr Andrea Malaspina
Dr Andrea Malaspina

Dr Andrea Malaspina (a member of our Biomedical Research Advisory Panel) also commented on the results. “EPA was found to accelerate the progression of MND when given at the pre-symptomatic stage in a SOD1 mouse model. To fully assess the potential risk of EPA further research is needed in other animal models, with different MND mutations (as different mutations cause different metabolic changes) to see if a similar effect is observed. At present we can only say that EPA accelerates the progression of MND in a SOD1 mouse model and it is not known whether it accelerates the progression of all forms of MND.”

For more information about the rare inherited form of MND please see our website

References: Yip PK, Pizzasegola C, Gladman S, Biggio ML, Marino M, et al.  (2013) The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis. PLoS ONE 8(4): e61626. doi:10.1371/journal.pone.0061626

The 11th Annual ENCALS meeting highlights how TDP-43 spreads in MND

The European Network for a cure of ALS (ENCALS) held its 11th Annual meeting in Sheffield from 31 May to the 2 June. The weekend was full of glorious British sunshine and more than 200 international scientists and clinicians were also able to enjoy a range of incredibly interesting talks about the latest developments in MND research.

A particular talk caught my attention on the first day by Dr Johannes Brettschneider from the University of Ulm in Germany. Dr Brettschneider explained how his research had shown the stages and spread of the protein TDP-43 in ALS (the commonest form of MND).

Dr Brian Dickie, Director of Research Development, said: “The key to defeating MND lies in fostering strong collaborations between neurologists, healthcare professionals, research scientists, early career investigators and students in the field of MND and the 11th Annual ENCALS meeting in Sheffield provided that opportunity. The MND Association was proud to support this event.”

‘Special’ staining

At the end of an afternoon of talks on the MND- causing genes C9orf72, FUS and SOD1, Dr Brettschneider engrossed over 200 delegates with his talk on the TDP-43 protein and how it spreads in ALS.

Although TDP-43 genetic mistakes are a rare cause of MND, scientists are especially interested in the TDP-43 protein because in the vast majority of cases of MND (irrespective of whether it was caused by an inherited genetic mistake), TDP-43 protein forms pathological clumps inside motor neurons.

The study (which is a collaboration between Dr. John Trojanowski and Dr. Virginia Lee from the Penn University Center of Neurodegenerative Disease Research in Philadelphia, America and the group of Dr. Heiko Braak in Ulm) used a technique known as ‘immunohistochemistry’.  This technique involves taking tissue samples of the brain and spinal cord from people who have died from ALS. The researchers would then make extremely thin slices of the tissue, which could then be stained using a ‘special stain’ and viewed under a microscope.

The stain used by Dr Brettschneider only ‘stained’ the TDP-43 protein in the samples, meaning that he could see the amount of TDP-43 in different areas of the brain and spinal cord.

Using the clinical information and TDP-43 staining this would allow Dr Brettschneider to stage the disease.

Image kindly provided by Dr Robin Highley, SITraN: (top left) a motor neurone with a skein-like neuronal cytoplasmic inclusion, next to a normal motor neurone (bottom left) on TDP-43 immunohistochemistry.
Image kindly provided by Dr Robin Highley, SITraN: (top left) a motor neurone with a skein-like neuronal cytoplasmic inclusion, next to a normal motor neurone (bottom left) on TDP-43 immunohistochemistry.

Axonal ‘telephone wires’ do more than just talking

Dr Brettschneider showed that TDP-43 increased in different areas of the brain and spinal cord during different stages of the disease. Amazingly, he also showed how ALS (characterized by clumps of TDP-43) spreads from one are of the body to another.

A motor neurone consists of three parts; the cell body, axon and nerve ending. The cell body contains the nucleus, or the control centre of the cell. When a message travels from the brain the cell body sends the message down the axon. Like telephone wires, the axon carries the message to the muscle, where the nerve endings cause the muscle to move.

However, in ALS it seems that these ‘telephone wires’ do more than just carry a message. The protein TDP-43 forms ‘clumps’ in the motor neurones and it seems that these clumps use the axon to travel from one motor neurone to the next (possibly explaining why someone get’s weakness in their arm and then their hand).

Another key finding was that TDP-43 clumps develop in the front part of the brain (prefrontal cortex), which is responsible for personality and may explain the development of cognitive symptoms.

Dr Brettschneider explained the importance of this research While spreading of disease-related proteins has been described for other neurodegenerative diseases like Alzheimer’s disease or Parkinson’s disease, this had not been previously shown in ALS. Now, we can show evidence that supports a spreading of the major disease protein TDP-43 in ALS across specific regions of the brain and spinal cord with ongoing disease.

 If these findings can be confirmed (for example in cell culture or mouse model studies) then this could lead to the design of new treatments specifically aiming to impair the spread of TDP-43 protein clumps.

Dr Johannes Brettschneider from the University of Ulm in Germany at ENCALS
Dr Johannes Brettschneider from the University of Ulm in Germany at ENCALS

Furthermore, we believe that our findings offer a better understanding of disease progression in ALS.  Our data implies that TDP-43 spreads throughout the prefrontal cortex with ongoing disease, thereby lending support to the idea that all ALS patients could eventually develop “frontal type” cognitive deficits.”

The future

Dr Brettschneider commented why this research is important to people living with MND explaining that “If these stages can be reproduced in patients with ALS they could offer a new way to assess disease progression and response to new treatments. We hope that our study provides the essential groundwork for strategies designed to prevent pTDP-43 spread.”

This research is only the beginning and more work is needed, Dr Brettschneider also explained what he hoped to do next with these exciting results. “There were restrictions in time and availability of the tissue samples during this study, so we were unable to determine how and where exactly ALS begins in the very early stage of the disease. Therefore, an important next step in our work would be to analyze very early cases with ALS to look at TDP -43 spread as this offers the most promising window for therapeutic intervention.”


Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Y, Kwong L, Lee EB, Elman L, McCluskey L, Fang L, Feldengut S, Ludolph AC, Lee VM, Braak H, Trojanowski JQ. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013 May 20. doi: 10.1002/ana.23937. [Epub ahead of print]

Twitter and MND

With over 140 million active users Twitter has grown up a lot since it arrived in 2006. This means that Twitter can be an extremely powerful tool for engaging, influencing and reaching out to a wide range of audiences across the world.twitter-bird-blue-on-white

Twitter is a social network (like Facebook and Google+) which allows you to network and engage with other users.

Anyone who knows me is well aware that I am a very keen advocate of Twitter. I believe Twitter is an excellent tool for engaging with, and getting people excited about science.

As a researcher Twitter can be used to promote and publicise your research (without having to travel to international conferences) and it also enables the public to raise awareness of important issues (like MND awareness month) and engage with the scientific and research community (@ALSuntangled)

As a researcher, Twitter can be used to promote and publicise your research (without having to
travel to international conferences) and find out what’s going on in your field – ‘listening rather than talking’ to your peers.
For more examples of why researchers should be using Twitter please see the post on our Research and Care Community Blog (ReCCoB) ‘Why you should be using Twitter’

Get involved

Our ‘Get Started on Twitter today!’ blog post also on ReCCoB explains how to join Twitter in five easy to follow steps. It covers everything from picking a name, deciding who to follow and sending your first tweet!

To get you started here’s some good examples of Twitter accounts to follow:

It’s OK to ask about MND research

The National Institute for Health Research (NIHR) has launched their ‘It’s OK to ask campaign’ which encourages patients and the public to ask about clinical research.

The campaign was launched on Monday (20 May 2013), ‘International Clinical Trials Day’ and the NIHR will be promoting this campaign throughout 2013/14.

“Clinical research is the way in which we improve treatments in the NHS. In many cases doctors will tell patients about research but we also need patients to ask about it and keep research at the top of the NHS agenda.” – NIHR website

Get involved in MND research

Mo LeCule the MND meerkat
Mo LeCule the MND meerkat

The NIHR is promoting the fact ‘it’s OK to ask about research’ and encourages patients or the public to ask their doctors about current research opportunities. The MND Association has a section on their website that lists ‘current opportunities to get involved in MND research’ and you can find out more here.

Getting involved in MND research does not only mean taking part in clinical drug trials. There are a number of other ways you can help including; questionnaires, tissue donation and fundraising.

“Last year, more than half a million NHS patients chose to take part in nearly 3,000 clinical research studies. Thanks to those patients, we are learning more all the time about how to deal with a whole range of medical conditions – and make some real breakthroughs that will improve thousands of lives.” – NIHR website

Share your experiences

The ‘It’s OK to ask’ campaign is encouraging patients or the public to share their experiences including what they asked and what response they received, via Facebook, Twitter (@OfficialNIHR #NIHRoktoask), phone: 0300 311 99 66 or email:

The C9orf72 mystery begins to unravel even more of its secrets

In 2011 an international team of scientists, including three MND Association-funded researchers, identified the elusive C9orf72 gene located on Chromosome 9. Since this ground-breaking discovery, researchers from around the world have been trying to find a way to open-up and reveal more about this MND-causing gene.

Determined to get inside and unravel the secrets behind C9orf72, the Association is funding a number of new and exciting research projects to help solve the mystery. These projects look at, not one, but a number of different aspects to try and understand more about C9orf72.

In order to solve this mystery our C9orf72 researchers are following the clues using zebrafish, mice, flies and DNA samples.

How the C9orf72 MND mystery began

We each contain copies of 23 pairs of chromosomes, including the X and Y sex chromosomes. These chromosomes contain thousands of genes that portray our characteristics such as hair and eye colour. These genes are made up of DNA which can either be ‘coding’ to make a protein, or ‘non-coding’. For details of how genes make a protein see our earlier blog post.

Before C9orf72 was identified researchers had focused on an area on Chromosome 9 that appeared to be connected with both the rare inherited form of MND and the related neurodegenerative disease frontotemporal dementia (FTD).

Using a number of cutting-edge techniques the international team isolated the C9orf72 gene expanded GGGGCC hexanucleotide repeat as being a crucial player in both inherited MND and FTD. Not only did the researchers find a link between MND and FTD, they also found that C9orf72 was found in approximately 40% of cases of inherited MND (where there is a strong family history). This means that we now know 70% of the genes that cause the rare inherited form of MND. For more details on C9orf72 see our earlier blog post.

For more information on inherited MND please see our website.

So, researchers found C9orf72. The next question was ‘What does it do? Is the gene defect repeat itself, or the protein it makes responsible for causing MND? And what goes wrong in MND?’

Following the clues to solve C9orf72

Two recent research clues

Since 2011 researchers have been trying to answer these questions and find out more about C9orf72. This has led to a dramatic increase in research, including two papers published in February and March this year!

Prof Christian Haass (Munich Centre for Neurosciences, Germany), who recently presented at our 23rd International Symposium on ALS/MND in December 2012, published a paper on the 7 February in the journal Science. The second paper lead by Prof Leonard Petrucelli (Mayo Clinic, USA) was published open access in the journal Neuron on the 20 February.

In a big surprise, both researchers found that the presumed ‘non-coding’ C9orf72 GGGGCC repeat expansion actually made a protein. Normally these ‘non-coding’ regions do not make proteins so this was a very big surprise indeed!

The researchers found that these proteins formed large clumps in the brains, and throughout the central nervous system (CNS), of people with C9orf72 MND and/or FTD. Importantly, they did not find these clumps in healthy individuals or those with other neurological disorders.

It is currently unknown as to whether these protein clumps are involved in MND and/or FTD, but they may be a potential biomarker or a therapeutic target in this most common type of MND. The next step is for the researchers to find out whether these proteins actually cause MND and/or FTD.

Finding more evidence to piece together the clues

In addition to these two papers looking into the mystery behind C9orf72, the Association is funding some exciting new research projects, each looking at different things, to further understand more about this gene.

Dr Johnathan Cooper-Knock
Dr Johnathan Cooper-Knock, MRC/MND Association Lady Edith Wolfson Clinical Research Fellow

Dr Johnathan Cooper-Knock (Sheffield Institute for Translational Neuroscience, UK) is already trying to identify how C9orf72 causes MND by utilising a genetic technique known as gene expression profiling. He is using samples from the Association’s DNA bank which are positive for the C9orf72 genetic mistake. Gene expression profiling is a technique which allows researchers to understand how the activity of genes contributes towards causing MND. (Traditional genetic studies are designed to look at which genes are affected, rather than their activity – ie when and how). Read more about Johnathan’s project here.

Developing new disease models enables us to understand the causes of MND and to test new therapies. One way to understand the function of C9orf72 and how this goes wrong in MND is to create a model. Our current research projects are developing new C9orf72 models in flies, mice and zebrafish.

Dr Frank Hirth (Kings College London, UK) will be producing a fly model, Dr Javier Alegre Abarrategui (University of Oxford) will be making a mouse model and Dr Andrew Grierson (University of Sheffield, UK) will be creating a zebrafish model.

All of these models aim to understand the function of C9orf72 and what goes wrong. The researchers hope to study what happens in MND and how this occurs by looking at behaviour and what happens when C9orf72 is ‘switched’ on and off. For more information about these exciting research projects please see our website.

Solving the mystery

All of our C9orf72 Association-funded research projects are using different approaches to look at C9orf72 in different ways as we are still unsure whether the protein or the repeat is the problem. From mice to flies all of these research projects together are helping to solve the mystery of C9orf72 and MND.

With the proteins formed by C9orf72 likely to be a potential biomarker or therapeutic target the two recent papers are adding to the growing number of clues, pointing researchers in the right direction to unravelling and solving the secrets of C9orf72.


Mori, K. et al. The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS. Science. 339(6125): 1335-1338. 2013 DOI: 10.1126/science.1232927

Ash, P. E. A. et al. Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS. Neuron. 77(4): 639-646. 2013 DOI: 10.1016/j.neuron.2013.02.004

Antisense seems to make sense

Results from a phase I clinical trial of a drug known as ISIS 333611 have been published open-access online in the scientific journal Lancet Neurology on 29 March 2013.

This is the first time researchers have tested the effects of delivering an antisense oligonucleotide directly into the human cerebral spinal fluid (the fluid between the spinal cord) showing that it is both safe and well tolerated in people with the SOD1 form of inherited MND. For information on inherited MND please see our website.

This work suggests that this ‘antisense’ approach may be a good strategy for other neurological disorders.

What is antisense?
Antisense is a type of therapy that causes the ISIS 333611 to directly interfere with the faulty instructions for making a SOD1 protein, thus stopping the production of the disease-causing substance. This is called ‘gene silencing’ as that part of the gene is not ‘heard’ when the final protein is made.

ISIS 333611 works by targeting mRNA, the ‘messenger’ that carries the genetic instructions from the SOD1 gene to the protein-making machinery (for more about mRNA and how proteins are made see our earlier blog post). Instructions in the mRNA for making the SOD1 protein (sometimes called a ‘sense’ sequence) are faulty in people with SOD1 inherited MND, which leads to harmful SOD1 proteins being made.

So if the levels of harmful SOD1 can be reduced, might this be protective? That’s the thinking behind the treatment. By binding to the SOD1 mRNA, ISIS 333611 prevents the production of a harmful SOD1 protein. Indeed, studies in SOD1 positive animal models indicated that reducing the level of SOD1 by antisense therapy increased lifespan. However, targeting the SOD1 gene in this way is a very ‘personalised’ treatment strategy – if it does work it will only work for people who have the SOD1 from of MND.

Results from the trial
Based on the encouraging animal studies, the researchers and ISIS Pharmaceuticals conducted a phase I trial of the antisense oligonucleotide ISIS 333611.

Twenty-one people with SOD1 MND were involved in the study and results from the trial have shown that there were no toxic effects due to increased dosing of the drug and that the drug was safe and well tolerated.

In animal models antisense therapy is found to spread well throughout the central nervous system (brain and spine). However, unlike animal models, the researchers showed that concentrations of ISIS 333611 were lower in the upper end of the spinal cord and brain compared to the injection site. Due to this the delivery site of the drug will probably need to be revisited in future trials.

Dr Pietro Fratta
Dr Pietro Fratta

As this was only a short-term ‘Phase I’ trial it was not designed to test whether this antisense therapy had an effect on MND. This would only be seen with long term treatment and future trials. However, the results are encouraging as they show that this type of therapy is both safe and well tolerated in people with SOD1 MND.

Results make sense

Dr Pietro Fratta (University College London), who is a recipient of a Medical Research Council/MND Association’s Lady Edith Wolfson Clinical Research Fellowship, has written an accompanying commentary on the paper. He said that this study “paves the way for applying antisense oligonucleotides to other forms of genetically determined MND” such as the C9orf72 form of the disease.

However, he stressed that “many hurdles still need to be overcome to bring this treatment to the clinic”.Dr Fratta also cautioned that the longer-term implications of lowering SOD1 protein levels had to be examined. The antisense approach not only targets the harmful mutated SOD1 protein, but will also lower levels of ‘healthy’ normally functioning SOD1, which plays an important role in protecting neurons from damage. So, the antisense treatment approach may be a ‘double-edged sword’ that will require very careful handling.

Miller, T. M. et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurology 2013 DOI: 10.1016/s1474-4422(13)70061-9 Read the full article here.

Fratta P. Antisense makes sense for amyotrophic lateral sclerosis C9orf72 Lancet Neurology 2013 DOI: 10.1016/s1474-4422(13)70059-0

Baking with proteins, mRNA and DNA

Each and every one of us is made up of thousands of different ingredients, which all combine together to create something amazing; life. Perhaps the most important of these are proteins.

Each protein in the body has its own special job to do. From making our muscles contract to controlling blood sugar, proteins are an essential ingredient in life.

In MND research we have identified a number of MND causing genes. These are genes that are found to be mutated in some people living with MND, which somehow causes the motor neurones to die. But, how does this happen? How does a gene form a protein? This blog post explains how an MND causing gene becomes a protein.

As simple as baking a cake

Here at the MND Association we love our cake. So, I thought what better way is there to describe how we make proteins?


Every cell in our body contains 23 pairs of chromosomes (46 in total), except for the egg and sperm cells that contain 23 chromosomes each.

Like a recipe book, these chromosomes hold all of our genetic material in the form of genes, in which everyone inherits two sets of (one from each parent).

Humans have approximately 24,000 genes, which each consist of their own DNA recipe to make a protein. Like cakes, proteins come in a range of different shapes and sizes, that come together to create you and me.

These DNA recipes are read by different cells to create the right protein for the job. For example, you would only make a wedding cake for a wedding, and the type of cake (chocolate or fruit) would depend on the wedding couple.

This is what happens in nerve cells (or motor neurones). A motor neurone will make a specific type of protein to help it grow, or to help it survive in low oxygen levels.

Following the recipe

A nerve cell creates a protein by finding the exact DNA recipe amongst the genes within the cell’s control centre, known as the nucleus. Once the recipe has been found the cell has a problem… The nucleus does not have the right tools to make a protein! The cell instead needs a specialised machine, or food mixer, which is only found outside of the nucleus called a ribosome.

In order to make the protein the DNA recipe needs to travel from the nucleus to the ribosome and this is done by means of a messenger. The DNA recipe can’t leave the nucleus so the cell ‘copies’ it into a messenger version, called mRNA.

The cell does this by removing certain parts of the DNA that do not affect the finished protein which are known as introns or ‘non-coding DNA’. This is known as ‘RNA splicing’ and is the same as removing raisons from a fruit cake. The cake is still made and still contains fruit, but the raisons are not essential in the finished cake.

mRNA can then travel the DNA recipe safely from the nucleus to the ribosome, where it can be finally made into a protein. Once made, this protein can then go on to do its specific job role (or in cake terms, be a wedding cake!).

ruined cake
ruined cake

Changing and ruining the recipe

Sometimes the DNA recipe in our genes can change through means of a mutation. Most of these are harmless spelling mistakes (sugarr instead of sugar) that do not affect the finished protein. However, sometimes these mutations can be so big and harmful (salt instead of sugar) that they do.

These kind of mutations are so big that the size, shape and structure of the protein can be changed – meaning that the protein can no longer do the job it was designed to do (our wedding cake is now no longer sweet and tasty, but ruined and salty!)

This is what happens in some of the MND causing genes. A big mutation occurs in the DNA recipe in a specific gene that causes the structure and shape of that protein to change. This change can then cause the proteins to ‘clump’ together in the motor neurones as they can no longer do the job they were designed to do.

Bake MND history
Bake MND history

Expert bakers

An understanding of genes and how proteins are connected is essential for understanding how they can go wrong in MND. The Association funds a number of exciting research projects investigating the MND causing genes, along with the proteins they form.

To help raise awareness of MND you can bake your own cake as part of our ‘Bake it!’ fundraising campaign. For more information and to request a fundraising pack please see our website.

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.

Zebrafish show that ‘connector neurons’ are the key in early stages of MND

A recent study by Motor Neurone Disease 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.

Dr Tennore Ramesh
Dr Tennore Ramesh

Zebrafish are ideal models for helping scientists understand what happens in MND. Unlike mice and fly models, zebrafish have transparent embryos which enable scientists to get a unique view of the developing neurones under a microscope! Scientists can also look at disease progression in adult zebrafish by looking at muscle strength and measuring their progress swimming against a current.

Not only are zebrafish useful for helping scientists understand what happens in MND, they are also an ideal drug screening model. Zebrafish and humans are more similar than you may think (see Kelly’s post) and potential new MND drugs can be screened quickly. Looking at how MND progresses in the zebrafish, before symptoms appear, can help us gain a better understanding of what causes the disease.

Motorways, dual carriage ways and slip roads

No, I’m not writing about travel alerts or the latest road disruptions due to flooding or snow. In fact, these road systems happen to be a perfect example of what interneurons are, how they relate to motor neurones and what goes wrong in MND.

Our body consists of two types of motor neurones, which are known as upper and lower motor neurones. The upper motor neurones are found in the motor region of our brain and connect to the spinal cord. The lower motor neurones are found between the upper motor neurones in the spinal cord and connect to the muscles (e.g. in the arms and legs). Interneurons are the vital connections between the upper and lower motor neurones.

Interneurons are the 'slip roads' between upper and lower motor neurons
Interneurons are the ‘slip roads’ between upper and lower motor neurons

When a signal is sent from our brain to bend an arm it starts by travelling down an upper motor neurone. The signal then travels to a lower motor neurone via an interneuron. When the signal from the lower motor neurone reaches the muscle in our arm it causes the muscle to contract and bend.

In MND these upper and lower motor neurones become damaged and they are unable to transport the nerve signal from the brain to the muscle in our arm. This means we are unable to contract and bend, even though the brain is telling it to.

­­­In our road system scenario the upper motor neurones are the motorways (e.g. the M1), and the lower motor neurones are the dual carriageways that link the motorways to nearby towns (e.g. the A38). In order for an upper motor neurone to send a signal (e.g. a car) to a lower motor neurone it needs to go via an interneuron, which in our road system scenario is a ‘slip road’ – making these interneurons vital connections between motor neurones.

This study has given us a better understanding of what happens in MND at the early stages of the disease (before symptoms occur). The researchers found that interneurons became damaged before the motor neurones themselves. Therefore this shows that interneurons are important in the early stages of the disease and scientists can begin to look at ways of preventing interneuron damage to see whether this has an effect on MND.

Adding more evidence to the puzzle

This study showed that, in zebrafish, interneurons are involved in the early stages of MND, which adds further evidence to previous work by another MND Association-funded researcher. Dr. Martin Turner (Oxford) also found damaged interneurons at the early stages of the disease before symptoms of MND occur in humans, with other studies showing interneuron damage in SOD1 mice models.

The next step would be to look at ways of preventing these interneurons from becoming damaged, to see whether this has any effect on the progression of MND.

This research is the first article we have paid to be made available Open Access, so that it is freely accessible to all. The article was published online in the prestigious journal ANNALS of Neurology on the 31 December 2012.

Paper reference:

McGown, A. et al. Early Interneuron Dysfunction in ALS: Insights from a mutant sod1 Zebrafish Model. ANNALS of Neurology 2012 DOI: 10.1002/ana.23780

One week to go until Chicago!

November has been an incredibly busy time for us, not because of Christmas, but because the 23rd International Symposium on ALS/MND is now only one week away! We’ve been incredibly busy building up for this year’s symposium including; preparing the final abstract book, promoting the #alssymp hashtag on Twitter and gathering enough information to support Belinda before she flies off to Chicago.

Abstracts, abstracts, abstracts!

As well as all of this, the abstracts were, for the first time, made available online, with free open-access, earlier this month. This was a milestone for us as previous years we just had hard copies of all of the abstracts available at the symposium. However, with advances in mobile technology and WiFi, this year it was decided that only the platform presentations would be available as hard copies during the symposium and all abstracts would be available online and free to view for all.

You can view and download the abstracts online now via our website.

Reporting LIVE

We, the Motor Neurone Disease Association, will be proudly reporting LIVE from the symposium through this blog. We will be reporting on a variety of interesting topics and talks so that you can be up to date with what is happening in terms of MND research.

If you want to follow the symposium on Twitter, you can do so by following the #alssymp hashtag.