A Summary of the news from the 23rd International symposium on ALS/MND

Each year we proudly organise the International Symposium on ALS/MND, and this year was a record breaker! The symposium was held in Chicago where over 900 clinicians, scientists and healthcare professionals attended the three-day event. With 86 international speakers and over 300 posters we managed to write about it all in just over 5,000 words in our daily articles on this blog.

Word cloud from our symposium reporting 2012. Created from wordle.net

Word cloud from our symposium reporting 2012. Created from wordle.net

Here’s a brief guide about what we wrote about along with links for the full articles:

Nature, nurture genetics and / or chance – what causes MND? Trying to understand what the different underlying factors are towards developing MND has always been a goal for ALS research. MND Association funded researcher and clinician Professor Ammar Al-Chalabi from King’s College London, gave a talk on this topic at the opening session.

Recognising and supporting the role of informal carers The symposium session ‘Carer and Family Support’ provided a platform to better understand the role that informal carers play in the lives of people with MND and discussed ways that we can improve support to carers.

A prize-wining story worth repeating Many congratulations to Rosa Rademakers from Mayo Clinic Florida USA, winner of this year’s Paulo Gontijo Young Investigator award. She won the award for her work on co-discovering the gene defect in C9orf72.

Mastering Pac-man Brian explains rubbish and recycling in relation to neurones after Prof Anne Simondsen’s talk where she described the ways in which neurones deal with their cellular rubbish.

The clinical trials session An update on the Np001 clinical trial, as well as the results from the NeuralStem safety trial.

Reflections on the poster session The two sessions felt quite different (‘a game of two halves’ is the phrase that comes into my head). At the first, there were lots of people there and lots of discussion. At the second, it was quieter, and more in depth, earnest conversations went on.

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

Reading the stars – why are ‘astrocytes’ toxic? A session uncovering the clues behind these support cells, and finding out as to why they are toxic to motor neurones.

Storify From the very beginning to the very end. From publishing the abstract book online to photos of presenters and their posters. See  the story of the symposium unfold with our storify.

The 24th International Symposium on ALS/MND will be held in Milan, Italy in December 2013.

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

Reading the stars – why are ‘astrocytes’ toxic?

On the last day of the 23rd International Symposium on ALS/MND in Chicago last week there was an excellent session on ‘the role of non-neuronal cells’ – it was an exciting session – below is a flavour of some of the topics discussed.

As its name suggests, motor neurone disease causes the degeneration of motor neurones – the long nerve cells that carry messages from the brain to the muscles via the spinal cord. But motor neurones don’t exist in isolation. Particularly in the last five years or so we have learnt a lot about the contribution of glia to the development of MND. In health, the different cell types that are collectively known as glia (eg astrocytes, microglia and oligodendrocytes) protect and support motor neurones. We know that this changes in MND. It’s an exciting and fast moving area of MND research, where there is lots still to find out. So it was a treat to have a session of the Symposium dedicated to the discussion of the latest results.

It opened with a great overview of what we know so far about the role of astrocytes in MND from Serge Przedborski. (Astrocytes are called astrocytes due to their star shape when seen down the microscope). Leading on from the studies showing that the medium (fluid) that astrocytes grow in can damage healthy motor neurones, he set out to find out whether astrocytes (and the chemicals that they emit) are toxic or whether there is a lack of benefit. (Bearing in mind glia are sometimes called ‘support’ cells – this comment about the lack of benefit is pertinent).

 Using a clever assay, where it is pulled through a filter by spinning it, he showed that the astrocyte medium is toxic. So the next question was, what is it in the medium that makes it toxic? He and members of his lab looked at many possible components to check for their toxicity to motor neurones. The studies took over two years and were all negative “it’s too painful to list them all” he commented. “I had to change approach as I was risking the health of members of my lab!”

As he was describing the new approach I was reminded of the guessing game ‘animal, vegetable or mineral”. Is it a protein? was his first question, then the next was ‘is there an overall positive or negative charge to the protein?’ (some of the protein building blocks – amino acids – have a positive or negative charge, so the use of charge is a common way to separate them) and finally ‘how much does this protein weigh?’. The answers to these questions provided the first sort through before a second approach narrowed the search for the ‘toxic protein’ in astrocytes down to a choice of just nine possibilities. After looking at all nine in more detail, he found that a receptor on the surface of the astrocyte known as DR6 was responsible for its toxicity.

Dr Dan Blackburn from the Sheffield Institute of Translational Research, UK, described another approach to uncovering clues about why astrocytes are toxic – using an approach that looks at which proteins are made at a particular time called ‘gene expression’ profiling.

 Although the genes in each cell are there all the time, they are not read all at once. (In the same way that you won’t try and make every single dish in your recipe book simultaneously). So looking at which genes are read (known as gene expression) over the course of the disease leaves a detective trail to find out what caused the motor neurones to die.

Following on from earlier work in their lab, Dr Blackburn presented the trail of evidence from when a mouse model of MND first begins to show symptoms, and from a later time point, when the disease is far more advanced. He pointed the finger at abnormalities in cholesterol transport.

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

Mastering Pac-Man

Growing up in a seaside town in the 1980s led to me spending a lot of my “formative years” in the local amusement arcades, playing iconic video games like Space Invaders (at which I was average) and Asteroids  (I was the kid to beat!). One game I never got the hang of was Pac Man, where you had to guide a munching yellow ball around a maze eating up lots of dots. I even bought a book ‘Mastering Pac Man’ which didn’t help much – I was just plain rubbish!

Pac Man chasing Dr Brian Dickie

Dr Brian Dickie and Pac Man

Talking about rubbish, fast forward 30 years and Prof Anne Simondsen from The University of Oslo is on the platform in Chicago describing the ways in which neurones deal with their cellular rubbish, such as poorly manufactured or damaged proteins.

Much as the dots are gobbled up by Pac Man, so cells employ a couple of basic ways to dispose of and recycle damaged proteins. One is a process called proteasomal degradation, which has been discussed on this website before by one of our guest bloggers, Prof John Mayer. However, some proteins, especially protein aggregates, are a bit too large and tough to be broken down by the proteasome, but they can be degraded by another process called autophagy – which can literally be translated as ‘self-eating’.

Prof Simondsen explained how aggregated proteins and even larger cellular structures can be packaged up for destruction by being encapsulated within membranes, forming structures called autophagosomes. These in turn seek out a structure called the lysosome, which contains digestive enzymes which break down the protein rubbish and keep the cell ‘spick and span’.

Using studies involving fruit fly models (a favourite model for cell biologists) she showed that the autophagy process declines with age, which is unfortunate because protein damage tends to increase with age. It was therefore no surprise that the level of autophagy in the brain was directly associated with the accumulation of protein ‘inclusions’, the health of neurones and the life expectancy of the flies.

Much of the evidence supporting a role for autophagy in neurodegeneration comes from the field of Huntington’s disease. Prof Simondsen explained how a particular mutated protein – called huntingdin – accumulates in the dying neurones and is a classic pathological hallmark of the disease. She demonstrated that autophagy normally plays a central role in the disposal of damaged huntingdin, but the system simply cannot cope with the amount of damaged protein, which starts to accumulate and literally ‘gunge up’ the cell. However, by stimulating the manufacture of additional autophagy machinery, the amount of aggregated protein can be reduced, helping to protect the neurones. This has so far only been shown in simple lab models of Huntington’s disease, but the encouraging results mean that further development to try and develop a treatment is underway.

So, could a similar approach be useful in other neurodegenerative diseases such as MND? Certainly, for some types of MND, such as those linked to a rare gene mutation called CHMP2B, it appears that a component of the autophagic machinery is impaired, which leads to protein build-up in cell models.

Dr Eiichi Tokada (Umea University, Sweden) provided further evidence that autophagy plays a role in disease progression in the SOD1 form of MND. By switching off a crucial component of the autophagy machinery, the disease progression in SOD1 mice was accelerated and their lifespan shortened. In addition, when he examined the spinal cords of the mice, he saw an increased presence of the characteristic SOD1 protein aggregates – a pathological hallmark of the disease.

Dr Faisal Fecto (Northwestern University, USA) provided evidence from a third genetic cause of MND. He showed how mutations in the Ubiquilin 2 gene disrupt the autophagy pathway by stopping the autophagosomes from linking up with the lysosomes.

So, it certainly seems that autophagy has a role to play in some of the rarer familial froms of MND. It remains to be seen to what extent it is involved in MND more generally, but it may mean that the potential treatment strategies being developed for Huntington’s disease may offer future opportunities for MND as well.

Our International Symposium website news stories:

International Symposium closes in Chicago

International Symposium focuses on clinical trials

International Symposium focuses on carer and family support

International Symposium begins in Chicago

Researchers unite at our International Symposium on MND

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