Zebrafish study provides innovative ideas for new treatment strategies

A study on zebrafish has increased our understanding of how motor neurones work and has provided potential clues for the development of future treatments for MND. The study, led by Dr Catherina Becker from University of Edinburgh, showed that a unique motor neurone repair system found in zebrafish can be enhanced if a particular signal called Notch1 is stopped. The results were published in the 29 February edition of Journal of Neuroscience.

What did they find?

Unlike us, zebrafish have the ability to regenerate motor neurones when they’re damaged. This means that zebrafish can provide scientists with an excellent tool to find out about motor neurone repair. A better understanding how zebrafish achieve neurone regeneration could provide clues to develop new treatment strategies for MND.

From their studies, Dr Becker and colleagues found that a chemical signaling pathway called Notch1 is increased when the neurones are damaged in zebrafish.

By over activating the Notch1 signal, they found that new motor neurones would not grow well, and would not grow in the same prolific numbers as normal. This means that an over active Notch1 signal can stop the regeneration of motor neurones that occurs in zebrafish.

To test whether the Notch1 signal could be counteracted, the research group treated zebrafish with an anti-Notch1 chemical to stop the Notch1 signal. This increased the generation of motor neurones.

As well as having a deeper understanding of the basic biology of how zebrafish regenerate their motor neurones, this study may help to provide new clues for the development of future treatments for MND.

This type of research is vital to lay the foundations for future studies. With a solid foundation of understanding of how motor neurones work, we can work toward identifying new and better treatments for MND.

What does this mean for people with MND?

This work is still at a very early stage of development. It unfortunately doesn’t mean that a treatment coming from this research will be available soon.

Researchers still need to identify whether developing a drug that can stop, or slow down the Notch1 signaling pathway would be a beneficial treatment strategy. To do this, researchers will need to carry out tests in a cellular, and animal models of MND. This is an important step, as it determines whether treatments are safe and effective before testing the treatment in people.

More information:

The Journal of Neuroscience, 29 February 2012, 32(9): 3245-3252; doi: 10.1523/JNEUROSCI.6398-11.2012

Official Edinburgh University news release.

Disappointing results from UK based lithium clinical trial

Yesterday, we announced on our website the disappointing news that the UK-based lithium clinical trial showed that lithium carbonate is ineffective at treating MND.

Commenting on the lithium clinical trial, Dr Brian Dickie, our Director of Research Development said:

“As many people will know, when lithium was first proposed as having benefit in MND, a couple of small, short-term trials were performed to establish whether the drug had a large and rapid effect on physical changes in disease progression. This trial, by contrast, was developed to ask whether the drug had a more subtle benefit over a longer time course, as is the case with riluzole, using survival times as the primary measure. The only way to answer this question was by performing larger, lengthier and more comprehensive studies.

“While the result is deeply disappointing, we now have a clear answer.

“Lithium can be described as a messy drug. It can act in multiple ways in the body, producing potentially beneficial effects as well as possible unwanted side effects. An overall beneficial effect, even modest, would have refocused scientific interest in the drug to try and separate ‘the good from the bad’ with the longer-term goal of developing more effective compounds. This is a strategy that is presently being pursued with regard to riluzole, in a project co-funded by the ALS Association, the University of Reading and ourselves.

“This trial was the first of its type in the UK, devised and run by clinicians without the need for drug company funding. A number of MND clinics that previously had little or no experience in clinical drug trials for MND have developed vital expertise and confidence in delivering trials to the highest standards. This can only help make the UK a more attractive place in the future for drug companies looking to push potential treatments from lab to clinic.”    

Two hundred and fourteen people with MND took part in this trial, each giving up their time to help find us the answers. We’d like to thank those that have taken part in this trial.

One person who took part in the UK lithium clinical trial was Colin Knight. We spoke to him a few years ago about his views on taking part. Please be aware that in the film clip, Colin speaks frankly about his diagnosis.

 

Read our official press release.

Cogane produces encouraging results in MND Association-funded study

Prof Linda Greensmith

Thanks to funding and some strategic ‘match-making’ by the MND Association, a new drug may have taken one step closer to beginning clinical trials in MND after producing promising results in an animal model of the disease.

The drug, known as Cogane, was developed by the biotechnology company Phytopharm. It had already demonstrated in laboratory tests that it could help to protect neurones by promoting the production of natural, nerve nourishing substances called neurotrophic factors and early animal testing had hinted at its potential beneficial effects in MND. However, its journey towards clinical testing in MND had hit a road block because it hadn’t been extensively put through its paces in large numbers of the most widely used animal model of the disease, the SOD1 mouse. Without robust data from this model, there would have been little to encourage further investment in Cogane’s development.

So up stepped the Association to introduce Phytopharm to Professor Linda Greensmith at University College London, a leading MND researcher with considerable expertise in SOD1 mouse testing. With funding from the Association, Prof Greensmith and her team were able to conduct a rigorous study of the effects of Cogane, administered to the mice after they had developed MND-like symptoms.

The drug produced some significant improvements in muscle strength and motor neurone survival and managed to produce positive effects even in mice that had reached the later stages of the disease. To give more substance to these preliminary but very encouraging results, the research team will now go on to the painstaking work of examining more closely Cogane’s effects on the motor neurones and other key cells that play a critical role in the progression of MND. 

After the disappointment of the Trophos trial results, it’s great to be able to share some positive news on the drug development front. We know from long experience that it’s wise to limit our excitement over positive results from the mouse model – after all, plenty of drugs have shown promise at this stage and have then gone on to fail in clinical trials. However, Prof Greensmith’s experience and expertise mean that Cogane will have been tested with the utmost rigor. As she herself commented, the results indicate that “Cogane has significant potential as a therapy for ALS and merits further evaluation”.  We don’t yet know what Phytopharm’s next steps will be – these may become clearer once the more detailed data from Prof Greensmith’s work have been published, which could take the best part of a year. Let’s hope that we have a given Cogane enough of a boost to push it out of the drug development ‘doldrums’.

Read the Phytopharm press release.

Our DNA bank appeal to feature on BBC Radio 4

Sunday 8 January is not only a celebration of Prof Stephen Hawking’s 70^th birthday, it’s also the date when the MND Association’s DNA bank appeal will be launched on BBC Radio 4.

Our DNA bank contains over 3,400 samples from people with MND and their families.  By using these samples scientists in this country have already made significant discoveries into the causes of MND. To advance research into MND we now want to make the DNA bank available to researchers across the world. To do this, we’re asking people to donate funds to the BBC Radio 4 charity appeal for our DNA bank. All money raised through the appeal will go towards maintaining the samples and making them accessible to worldwide researchers. It will take a global research effort to beat MND, and the DNA bank is a very important tool in the fight against the disease.

Samples from the DNA bank will help scientists identify genes that cause familial (inherited) MND or those that influence susceptibility to sporadic MND. This will offer crucial insight into the causes of MND. Understanding the causes of MND will lead to the development of new treatments.

To listen to the broadcast narrated by Joss Ackland, listen in on Sunday 8 January at 7:55am or 9:26pm to BBC Radio 4. This will also be repeated on Thursday 12 January at 3:27pm, or you can listen again after the broadcast.

More information:
DNA bank samples are currently being used in a number of studies investigating the causes of familial and sporadic MND. For more information, please see the DNA bank pages of our website.

If you contributed a sample to our DNA bank, you can find out more about what happens to samples after they’re donated in our information sheet, and in our Thumb Print article from 2010.

Read our press release on this story.

Happy New Year – Quiz answers and round up of 2011!

And the answers to our Christmas Quiz are:

1. How many neurones does a human have? Billions
2. Which animal has the largest brain? Bottlenose dolphin
3. How much does a human brain weigh in comparison with our total average body weight (in percent)? 2
4. How many DNA samples does the MND Association’s DNA bank hold? 3,400
5. How many research projects do we currently fund? 44
6. How much does our research project portfolio currently come to? £7.6m
7. How many PhD studentships do we currently fund? 12
8. How many times a year do we have research grant funding rounds? 2
9. How many unproven MND treatments have ALSUntangled investigated so far? 13
10. How many stem cell research projects do we fund? 2

At the beginning of a new year, it’s always encouraging to look back on how far we’ve come. The list of MND research achievements continues to grow exponentially every year, and I’m pleased to say that last year was no exception, demonstrating that we really are living in exciting times.

2011 had some important discoveries in the world of MND research to find the answers to what causes MND. A number of MND causing gene mistakes were discovered including C9ORF72, Ubiquilin2 and SQSTM1. With these findings, we now know the cause of approximately 70% of cases of inherited MND – a massive leap from approximately 25-30% of known genetic mistakes the previous year.

Within the team, we’ve also made some promising headway toward our aims set out in our research strategy, by funding and promoting cutting edge research both within the UK and around the world. For example, our groundbreaking biomarker project led by Dr Martin Turner at Oxford yielded its second set of promising results, just three years into the five-year project. Dr Martin Turner also gave an enthralling talk at last year’s International Symposium on ALS/MND on neuroimaging (brain scanning) and he’s regarded as ‘the man’ to speak to in terms of MND neuroimaging on an international level.

As well as the research projects that we fund yielding positive results, and following progress on an international level, we’re also a major player in promoting research. The key to defeating MND lies in fostering strong collaboration between leading researchers around the world  and sharing new understanding of the disease as rapidly as possible. In 2011, we made two huge steps in this:

In January 2011, in conjunction with two leading members of the International Consortium of Stem Cell Networks (the Canadian Stem Cell Network and the UK Stem Cell Network), The New York Stem Cell Foundation and the ALS Association of the USA, we organised an MND stem cell conference. Our workshop brought together 60 of the world’s leading stem cell research experts to shape the development of future international MND stem cell research and to form new research collaborations. We were privileged to organise this event and the research community now have a solid foundation of understanding of where we are in terms of MND stem cell research. Dr Brian Dickie, our Director of Research now also has the honour of being a co-author on the scientific paper from the conference – published in the journal ALS.

In July 2011, we made a further step forward in sharing new understanding rapidly by joining a group of research-funding organisations to fund UK PubMed Central, an online research database containing over two million research articles. This is the first step in the Association’s aim to establish a comprehensive resource for the global MND research community.

We also had a fantastic year for improving the way we fund research and maintaining our high standards.

For our first grants round of the year, a record-breaking 19 full applications were considered for funding by our Biomedical Research Advisory Panel. Only one in five research applications is considered of a high enough standard for funding, but through our rigorous process we can provide our donors with the assurance that they are supporting the ‘very best of the best’ MND research.

Before our second grants round, we announced the successful launch of our online summary application form for researchers applying for grants and PhD studentships. By evolving our summary application process to use an online system, we are able to ensure that our high standards are maintained and that we are using our time efficiently and effectively to fund high-quality research.

We also proudly received our certificate for best practice for our rigorous procedures for funding research from the Association of Medical Research Charities (AMRC) in the UK with a comment saying that we are “considered as setting the standard within the audit”.

You can find out more information on the research projects we currently fund on our research we fund information sheet.

One of our highlights from last year, and the result of over a year’s work in preparation from the research team and our conference team, was the International Symposium on ALS/MND held in Sydney, Australia. We are proud to organise this vital worldwide event every year, and are pleased that last year was successful. Holding the event in different countries around the world enables us to draw new people into the international research community, bringing new ideas and expertise to the field and creating new alliances in the fight against MND.

We took you behind the scenes of last year’s symposium by writing daily blog articles on a multitude of topics. If you’ve not already read these, you can find an introduction to these with links on our blog. Please remember to complete our survey on what you thought of our reporting, as it really helps us to determine whether we should continue to report from the symposium, and whether we should change anything.

We’ve definitely set the bar in 2011 and have a lot to live up to in 2012. We’re really looking forward to see what 2012 holds for MND research, and we hope that you’ll continue to follow our progress on our blog throughout the year.

We wish you a very Happy New Year from all of us in the Research Development Team at the MND Association.

Another recycling bounty hunter linked to MND

In the short space of three months, details of a second gene have been published linking MND to the protein recycling system in our cells.

Leading this research was Prof Teepu Siddique, eminent MND researcher from North Western University in Chicago USA. Not only was he the founder of the first MND causing gene SOD1, but he also led the group that identified faults in the UBQLN2 gene in MND in August 2011. This research was published in the November edition of the Archives of Neurology journal.

We’ve invited Prof Siddique to give a plenary talk at this year’s International Symposium in Sydney, Australia from 30 November to 2 December 2011, at which we believe he’ll be discussing these exciting new advances!

What did they do?
Instead of searching for common genetic mistakes in families with the inherited form of MND, this research group focused on a candidate gene called SQSTM1. They chose SQSTM1 as a candidate due to the prior knowledge that its protein product is associated with MND.

They then unravelled the code for this particular gene in 340 people with the rare, inherited form of the disease and 206 sporadic cases of MND. They also compared these with 738 healthy controls.

They identified 10 different mistakes in the SQSTM1 gene in 15 people and did not find any of these mistakes in the healthy controls. The research group therefore estimate that genetic mistakes in the SQSTM1 gene could account for approximately 2-3% of cases of MND.

However, it is not yet conclusively known whether these mistakes cause MND, or increase the risk of somebody developing the disease. Further studies are therefore needed to confirm this.

What does SQSTM1 do?
The gene SQSTM1, holds the instructions for a protein called P62, otherwise known as sequestosome 1. 

The P62 protein can be thought of as a ‘bounty hunter’ of proteins that need to be recycled inside motor neurones and other cells. When given instructions to find proteins waiting to be recycled, it seeks them out and delivers them to the cells recycling system.

P62 has a related role to ubiquilin 2 (UBQLN2 which we wrote about in August) as they both work in the protein recycling system within the body.

This research therefore further implicates that the protein recycling system is faulty in MND.

The next steps with this story, is for researchers to confirm whether mistakes in the SQSTM1 gene cause, or contribute to the disease in other populations around the world. They will also need to investigate how the protein recycling system can go wrong in MND to be able to develop new treatments that can target these processes to slow down, or stop the disease.

More information on the protein recycling system:
Last month, Prof John Mayer from University of Nottingham, who is the Chair of our Biomedical Research Advisory Panel, took us behind the scenes of the protein recycling system on our research blog

Read our press release.

Reference: Fecto F et al. Arch Neurol. 2011; 68(11):1-7

Chromosome 9 finally reveals its secrets

It’s taken a huge international collaboration, including 3 MND Association-funded scientists, to discover a genetic mistake that appears to cause almost 40% of cases of familial (inherited) MND – that’s nearly twice as many as are caused by mutations in the SOD1 gene and more than three times as many as are caused by TDP-43 and FUS combined. Yet despite the fact that it’s relatively common, the rogue gene proved especially difficult to find.

Digging for genes

Our genetic code is arranged into 23 pairs of subunits called chromosomes. Earlier work had homed in on an area on chromosome 9 that appeared to be significantly associated with both MND and the related neurodegenerative disease frontotemporal dementia (FTD), but nobody could drill down as far as the problem gene itself. As a result, chromosome 9 became something of an ‘archaeological dig site’ for MND researchers, with several groups using cutting edge techniques to try and excavate the elusive causative gene that they knew was lurking somewhere in the short arm of this chromosome. The successful international team, which included almost 60 scientists at 37 institutes, finally discovered the exact location and nature of the aberrant genetic code by looking in the most unlikely of places – in the stretches of DNA that do not actually provide any instructions for building proteins, otherwise known as non-coding DNA.

What did the researchers unearth?

The research team studied DNA samples from a Welsh family affected by inherited MND and FTD that was already known to be associated with chromosome 9, as well as samples from a similar Dutch family and a large number of Finnish inherited and non-inherited MND cases. In among the non-coding DNA in a chromosome 9 gene called C9ORF72, the researchers found a 6-letter genetic ‘word’ which, in healthy individuals, is consecutively repeated up to about 20 times. However, in the Welsh and Dutch families and a large proportion of the Finnish familial cases, the 6-letter word was repeated as many as 250 times. This phenomenon is known as a ‘repeat expansion’. The researchers went on to check for this repeat expansion in familial MND cases from North America, Germany and Italy, and found it cropped up in 38% of them. They even found it in a much smaller proportion of sporadic cases from Finland, suggesting that it could be an important risk factor in at least some people with the  non-inherited form of the disease.

What does the discovery mean for MND research?

Despite the fact that the repeat expansion does not directly affect the instructions for building a protein, there is good reason to believe that it can still lead to significant neuronal damage. At the moment it is not fully understood how this happens, but one possibility is that it leads to the production of excessive and consequently toxic quantities of RNA, the molecule that provides the cell with a more usable copy of DNA. Disruption to RNA processing has already been implicated as a disease mechanism in MND – this is the pathway through which faulty TDP-43 and FUS are thought to exert their effects – so C9ORF72 may provide scientists with another piece of the RNA jigsaw.

The effect of the repeat expansion is clearly open to influence. Among those people with the repeat expansion, some experienced only FTD, others showed only muscle weakness, and some had both MND and FTD.  The reasons for this variation in symptoms will be just one area that scientists will now want to look into. This overlap between MND and FTD is something that researchers are very keen to understand, and the C9ORF72 discovery may be the key to solving this puzzle. They will also want to better understand how the repeat expansion causes damage, and that will include trying to find out what C9ORF72 actually does – at the moment this is unknown. (Maybe it’ll get a more interesting name along the way!) Building on the new finding in this way could help move us closer to an effective treatment.

For now, a more tangible consequence of the discovery could be a genetic test for people already diagnosed with familial MND who want to understand more about the basis of their disease. Such a test will take a little time to develop but should become available in the UK in the next few months. When it does, it will be accessible to genetics labs across the country. Anyone interested should speak to their doctor or specialist nurse.  

Dead heat

Just as archaeologists might question whether a newly discovered artefact is the real thing, so scientists need double-checking when they claim to have made a new discovery. Fortunately, a second team hit upon C9ORF72 at exactly the same time, and their results will be published alongside the work described here, in the journal ‘Neuron’. The race to the ‘Lost Ark’ of chromosome 9 ended in a tie, but has provided the research community with a major piece of the MND puzzle on which to build future discoveries.

Article: Renton A, Majounie E, Waite A et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked amyotrophic lateral sclerosis-frontotemporal dementia. Neuron (2011).

Read our press release on the C9ORF72 story.

New gene finding suggests recycling is key to all forms of MND

Researchers from Northwestern University Feinburg School of Medicine in America, have identified that faulty ubiquilin 2 plays an integral role to MND.

Led by eminent researcher Prof Teepu Siddique this research group describes unique mistakes in a gene called UBQLN2, which codes for a protein called ubiquilin 2, in five families with the inherited form of ALS. This research group also found that this protein is found in both the inherited and sporadic form of MND, which suggest that this finding could be key to finding a new treatment for the disease. Their findings were published in the prestigious Journal Nature.

What did the researchers do?

The researchers started by identifying a novel genetic mistake in a gene called UBQLN2 for a family affected by the inherited form of ALS. ALS is the most common form of MND. They went on to duplicate this finding by identifying four more genetic mistakes in the same gene in four other families with inherited ALS. This verified that this finding is not simply a ‘one off’.

By examining post-mortem spinal cord samples from people with ALS within these families, faulty ubiquilin 2 was identified as being involved in forming ‘tangled lumps of proteins’ within their motor neurones. When a researcher looks down a microscope at a motor neurone with the disease this ‘tangled lump’ is a classic sign of MND.

The next question that this research group addressed was whether ubiquilin 2 could also be found in other forms of MND. Remarkably, by studying post-mortem samples of people with the randomly occurring ‘sporadic’ form, inherited form (caused by mistakes in SOD1, TDP-43, FUS or an ‘unknown’ gene) and fronto-temporal dementia – related MND, they identified ubiquilin 2 within the ‘tangled lump’ in all of the samples.

This means that ubiquilin 2 could be the ‘smoking gun’ of MND.

Never before has one single protein or gene been related to all forms of ALS. Until now.

Mistakes in this gene are very rare and as yet, we don’t know how many cases of inherited MND are caused by it. This discovery does not open up the possibility of a new genetic test to identify people who might be at risk from the disease, but it does provide a new and exciting insight into the causes of all forms of MND.

How does ubiquilin 2 cause MND?

Imagine a world where all recycling collectors are on strike. Every Wednesday at 7am you place a box of recycling on your driveway ready to be collected, but it’s still there in the evening. The next week you put out more recycling, and that isn’t collected either. After weeks of putting your recycling outside, you notice that the pile is mounting and still isn’t being collected. This doesn’t bother you too much as you can still step over it, albeit in a slightly slower manner. A few months pass and you can no longer get out of your driveway as it’s covered by recycling. Now you can’t get rid of your rubbish, you can’t get to work and you can’t even leave your house all because of the pile up of recycling. The same thing is happening to everybody all over your town. This is what happens in MND.

One of the pathological hallmarks of MND is a build-up of ‘recycling bins’ of proteins in motor neurones. Normally, these recycling bins are emptied on a regular basis by a process regulated by a family of proteins called ubiquitins – of which ubiquilin 2 is a member. This build up of recycling causes pandemonium in cells, as vital movement of nutrients around the cell cannot easily pass to where they need to get to, causing an additional burden to the motor neurones. Eventually, the motor neurones start to degenerate because of this.

What now?

These results will now need to be verified in more people with MND. However, this study could revolutionise the MND research world and provides evidence that the recycling pathway plays a crucial role in MND. Researchers now need to find out how the recycling pathway is involved with MND which could provide insights into how new treatments could be developed to target the disease.

We’ll be keeping a close eye on ubiquilin 2 in the future!

Read our press release on this news story.

Read the Scotsman article on this story.

Reference: Nature (2011) DOI:doi:10.1038/nature10353

UPDATE: Prof John Mayer from University of Nottingham takes you even further behind the scenes of this news story.

Medical research should start and finish with the patient

Results of a recent poll suggest that the UK public is incredibly supportive of healthcare research within the NHS. These results will now be used as evidence that the developing Health and Social Care Bill should include statements about an obligation to fund and promote research within the NHS.

The results published today, state that a staggering 97% of people polled believe it is important for the NHS to support research into new treatments for patients and 92% believe it’s important for the NHS to support such research funded by charities.

990 adults were polled to find these figures, by one of the top polling agencies in the world, Ipsos MORI. They were commissioned by the Association of Medical Research Charities of which we are a member, Breast Cancer Campaign and the British Heart Foundation.

Commenting on the poll results, our director of research development, Dr Brian Dickie said that “The overwhelming support demonstrated in this poll indicates the importance that patients and public place on clinical research. Considerable advances are being made in understanding complex diseases such as motor neurone disease and the NHS will play a vital role in translating this new knowledge into better diagnostics and potential treatments. Medical research is no different from medical treatment in that it has to start and finish with the patient.”

 We’ve known for a long time that people affected by MND place research high on their priority list and one of our aims is to enable people with MND to participate in research should they so wish. In order for us to achieve this, we will need the right infrastructure available within the NHS to support healthcare research – studies that involve people such as clinical trials, biomarker studies etc.

We’re currently funding a number of healthcare studies within the NHS that involve people with MND altruistically giving blood samples, answering questionnaires and having brain scans to bring us closer to understanding the causes and developing new tools for a quicker diagnosis.

One study we’re currently funding is trying to identify a specific MND ‘fingerprint’, known as a biomarker to speed up the diagnosis of MND. The study is called Biomarkers in Oxford (BioMOx) and is led by Dr Martin Turner from the University of Oxford, from within the John Radcliffe Hospital in Oxford. People with MND play a crucial role in this project.

Speaking about his project, Dr Martin Turner said that: “My sort of research simply can’t be done in a different model, either in a test tube or in a culture dish. It has to be based in patients. We recognise that we are asking them to come and do things that don’t directly benefit them, we’re not giving them a treatment, but it helps us to find out more about the disease. I never cease to be humbled by how much time people with give and what they’ll have done towards our goal of finding better treatments.”

It is vital that the NHS continues to support healthcare research, and to ensure that diseases, such as MND are not forgotten.

The results from the poll are a clear indicator that healthcare research should lay at the heart of the NHS, and should be stated in the developing Health and Social Care Bill.

Making our voice heard

We will continue to make our voices heard to ensure that MND care and research can thrive in the future so that we can move closer to finding a better treatment, and speeding up the diagnosis of MND.

If you’re interested in reading more about our campaigning activities and want to get involved, then please visit our campaigns website : http://mndcampaigns.org

Read our press release

Read the AMRCs press release

Read about Dr Martin Turner’s Biomarker study

Painting the way to new motor neurones from stem cells

A study led by MND Association funded researcher Prof Siddharthan Chandran from the University of Edinburgh has developed a new method to create a diverse group of motor neurones from stem cells. The research, published in the journal Nature Communications could be used to create more accurate and clinically relevant laboratory dish models to learn more about the differences in vulnerability and connectivity of motor neurones in MND.

 Why are the subtypes of motor neurones important to MND research?
When we first start to develop as embryos in the womb, chemical messages are used as cues to tell our cells what to turn in to. At the start of this process our cells can be thought of as blank canvases that have the potential to turn into any type of cell. Mixtures of ‘colourful’ chemicals are then used to create a unique ‘hue’ signal in order for the cell to know what to become.

So, depending on the ‘hue’ of chemicals around them, neuronal precursor cells will turn into different subtypes of motor neurone. In their fully formed state, these motor neurones subtly vary in their chemical makeup (due to acting on the different ‘hue’ signals given), their vulnerability to degenerate in MND, as well as the way they connect and communicate with other cells.

The subtle differences in subtypes of motor neurone have not been replicated in a laboratory dish model of MND to date. However, being able to develop such a model would provide MND researchers with a true spectrum of the way that MND affects the different subtypes of motor neurones. They would then also be able to develop new and better treatments that can target specific types of motor neurones that may be more vulnerable to MND.

What did the researchers do to find this?
The collaborative research group from Universities of Edinburgh, Cardiff and Cambridge tested a new method for creating different types of motor neurones in a dish from human embryonic stem cells.

To do this, they first added a chemical that accelerates the process of turning stem cells into neurone precursor cells – it’s the equivalent of being able to add a ‘quick drying’ additive to a painting. By adding this chemical, which has been given the catchy name of SB431542, the process of changing an embryonic stem cell into motor neurone progenitor cells is sped up from approximately 30 days to just 12 days.

They then tested whether a certain chemical called ‘retinoic acid’ is needed for the process of making different types of motor neurone. By measuring the chemical makeup of the functional motor neurones produced without retinoic acid, they were able to determine that they had produced a different type of motor neurone that is different from those created with the use of retinoic acid.

What’s next?
By defining a new process to create new and better models using stem cell technology, a new multi-motor neurone type model could be created for MND to study the similarities and differences between motor neurones in MND.

By learning more about these differences, we could learn more about how and why some motor neurones remain spared in MND.

To find out more about the future of stem cell research, please read Dr Brian Dickie’s account of the recent stem cell conference. Or, download a copy of our stem cell information sheet.

Journal Reference: Patani, R. et al. Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nat. Commun. 2:214 doi: 10.1038/ncomms1216 (2011).