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 

Reflections on the poster session

In Chicago, it’s the beginning of the third day of the International Symposium on ALS/MND. I feel that I’ve become almost institutionalised: I get up, have breakfast and head down to the ‘Ballroom’ floor of the hotel. After saying a few hellos, I’ll head to my chosen session, settle down, get my notepad out and open my ears.

I’m really looking forward to hearing an update on the role of non-neuronal cells this morning. The opening speaker, Serge Przedborski, from Columbia University USA, is a name I’ve been reading on the top of research papers for years. So it will be great to hear what he has to say.

Poster session delegates

But before I head down there, I’m trying to unravel the blur of new ideas and people that I met yesterday, so I can tell you about them. It’s quite hard to remember who I heard when and recall the thing that made me sit up and scribble more furiously than before. I wanted to write more, but found myself writing lots about the posters and not finishing this until after the non-neuronal cell session – which lived up to expectations by the way!

Yesterday morning began with the poster session. It was the second poster session of the meeting, the first was on the evening of the first day. 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. At the second session it felt like, ‘ok we’ve done all the meeting and greeting, now let’s get down to the business of looking hard at the wealth of information that’s here to be digested’.

On Wednesday evening, my first concern on entering the room was ‘Has everyone put their poster up?’, ‘Can delegates find their way around?’, ‘Is there enough space to get past / light to read the poster?’ I spent most of Tuesday setting things up for the poster session – so I’m seeking reassurance!.

At allotted times throughout the two sessions, presenters are required to attend their poster – to give other delegates on opportunity to discuss their results, methods and interpretations. The times are printed in the programme for the meeting – so if there’s someone you definitely want to talk to, catching them at their poster slot is a good bet. That’s particularly true this year with over 900 people attending. Once I’m reassured that it all looks to be working well, I started to head to the part of the room where I know the presenters will be standing by their work.

The room is literally buzzing with people talking about MND research and the clinical management of the disease. There are lots of people here, many that I know and haven’t spoken to yet! So I stop to have a chat, see how their work’s going. I take the ideas that one researcher has told me and carry them along to a poster a few metres down the room. I quite often find myself asking, ‘So, how does your data compare to poster X’ or ‘Poster Y / person Z is looking at a similar area, have you spoken to them’. Before I know it, the sessions come to an end – and / or I’ve hit a wall where I can’t digest any more science – and I didn’t get to see the posters I was really interested in reading.

Poster session delegates

On my second visit, I’m a lot more focussed, but even then, I find myself getting disctracted in lots of interesting ways. Which is how I came to have a conversation about the costs of getting a genetic test in USA. Until a year or so ago genetic tests for MND weren’t part of a medical insurance packages. Thank goodness for the NHS, making decisions about whether to undergo a test to see if you carry a gene for MND in those rare cases where there is a family history of the disease are difficult enough, without having to consider whether you can afford it too. Another ‘chance’ poster was learning about a novel, and very new, way of managing dysarthria. The neurologist explaining this data gave me a quick tutorial on what happens in dysarthria: basically the closure of a passage between the nose and the throat doesn’t function properly – air escapes up to the nose when speaking, but also when breathing in (the latter means that less air gets to the lungs)(P25 in the abstract book if you want to know more). This can be corrected by putting in a plate (a bit like the plates that are used for false teeth), but this is poorly tolerated by people with MND. So, trying a method that has worked for non-MND patients that have a similar problem, Dr Storck from Switzerland, and colleagues have used a fat transplant, to help this passage way close more effectively. It’s early days, its only been done in three patients so far, but they report a positive effect.

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 

The clinical trials session

A very much ‘must report on’ session of the 23rd International Symposium on ALS/MND was the clinical trials and trial design session. There are many reasons that make this an interesting session – perhaps the most eagerly anticipated were the presentations on the NP001 study and the results of the stem cell safety trial:

NP001 update

We reported on the blog on 1 November the results of the NP001 study, and these findings were confirmed today by Dr Bob Miller from Forbes Norris Centre in California USA. The trial showed that intra-venous administration of NP001 was found to be generally safe and well tolerated, with a modest clinical benefit seen in the high dose (2mg/kg) group.

As previously reported in their press release, ‘post-hoc analysis’ (meaning literally after the event), showed that some patients in the higher dose group did not have any change of a scale that measures the functional capabilities of people with MND called the ALS-functional rating scale (ALSFRS) over the course of the study. Historical controls were used in the post-hoc analysis – the first time that the US Food and Drugs Administration (FDA) had allowed them to do this.

The room was packed and there were five people queuing to ask questions about this talk. Questions were asked about the use of historical controls; the possibility that patients would identify that they were in the treatment group due to the presence of a ‘burning feeling’ at the injection site; and about other forms or ways of taking NP001. On the last of these points, a question about the chemical structures of NP001 and WF10 went unanswered.

But Dr Miller was categoric about different ways of taking NP001. “Taking NP001 in any other route [than intra-venously] is unsafe and unproductive”.

Results of stem cell safety trial

The first regulatory body (FDA) approved phase I safety trial of a stem cell treatment for MND, conducted in America, is now complete. Dr Johnathan Glass from Emory ALS Center, Georgia USA presented the results of this study.

In the last 5-10 years there has been a huge amount of interest from MND researchers, clinicians and patients alike about the possibility and potential for using stem cells to treat MND. More information about what stem cells are and how they might help is available on the MND Association’s website.

As for any other drug or potentially beneficial intervention, the first part of the assessment should always be to obtain a robust and objective measure on whether such a treatment is safe, and this is what the NeuralStem study was designed to find out.

A team of highly trained specialists, in close consultation with the FDA, designed a study to look at the safety of giving an injection of stem cells directly into the spinal cord of people with MND. Eighteen surgeries were performed on fifteen patients – three of these patients volunteered to have two surgeries (two injections).

The first three people with MND recruited into the study received a single injection of stem cells on one side of the bottom (lumbar) of the spinal cord. The next three received injections on both sides of the lumbar spinal cord. These first six patients were at an advanced stage of MND, where they were unable to walk.

The next six patients, who were able to walk, received injections at one or both sides of the lumbar spinal cord. The last three patients received a single injection higher up the spinal cord (cervical) and finally, the three patients able to walk who received a single lumbar injection underwent a second surgery to receive a single cervical injection.

The results from the first six patients has already been published in a scientific paper:

Stem Cells 2012 30(6) 1144 – 51

Dr Glass concluded that the procedure is well tolerated and safe and that there is no indication that the surgery accelerates the progression of the disease. The next phase of the study, giving injections into the cervical spinal cord at increasing doses (numbers of cells) is funded and is awaiting FDA approval.

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 

A prize-winning 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.

As part of her prize (in addition to a medal and a cheque to continue her work) she gave an overview of the research at the opening session of the 23rd International Symposium on ALS/MND. The story was one of looking in some unusual places as well as all the obvious places to locate a gene defect had been thoroughly searched by researchers around the world. Dr Mariely DeJesus Hernandez in Dr Rademakers lab spotted something odd about the way the C9orf72 gene was inherited from the respective parents of someone with MND. She should’ve seen the copy from the mother and the copy from the father, but using their usual laboratory experiment, a copy of the gene from one of the parents wasn’t found.

One explanation for this unusual finding was that there was a ‘repeat’ sequence – that the experiment she’d run wasn’t set up to find. So, thanks to all the previous reports in the literature, Dr Rademakers and colleagues tried a lab experiment that other people had used to detect repeat sequences in other (ie non-MND) diseases. Use of this new lab experiment led to them identifying the presence of a long repeat in people with MND but not in unaffected people.

After a brief history of the discovery of this important gene defect, Dr Rademakers went on to give an overview of research around the world. It was interesting to see that this has worldwide significance. She showed a graph representing the percentage of cases of people with a family history of MND where C9orf72 had been discovered. The bottom line was that C9orf72 repeats are found in 34% of people who had MND with a family history of the disease and in 26% of people who had FTD with a family history of the disease.

But although much has been achieved in identifying this gene defect and the colossal amount of work worldwide since its discovery, in her final slide, Dr Rademakers reminded us that there’s much still to be done. For every concluding comment there was a list of two or three questions that the new information provoked.

This talk was an excellent starting point for a topic that was and will be repeated many times (pun intended) through the International Symposium.

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

Lets talk together

Dr Rick Bedlack, founder of ALSUntangled speaks at the International Symposium about assisting patient choices. Dr Belinda Cupid, from our Research Development Team explains more:

Neurologist and natty dresser Dr Rick Bedlack, from Duke ALS Clinic in North Carolina USA, took on a challenging topic of patient decision making at this afternoon’s session of the 23rd In ternational Symposium on ALS/MND from the perspective of different decision making models.

In quite a philosophical talk, he framed the discussion of the different models of doctor – patient relationships from a discussion that he’d had with one of his patients. An educated patient accepted Dr Bedlack’s offer of riluzole and management of their care through a multidisciplinary team care approach, but declined to participate in a research study. The patient explained that they were going to pursue an unproven treatment that they’d heard about. Dr Bedlack commented that “their decisions bothered me and I started to think about why they bothered me”.

Starting with their refusal to participate in clinical trials, from one perspective, slower enrolment…

View original post 369 more words

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 of the 23rd International Symposium on ALS/MND in Chicago. A record number of over 900 delegates gathered to hear his overview of where we are. It was a clear, informative, humorous talk with added technical wizardry!

“People say that this looks like Voldemort, but actually it’s me!” he commented on showing a whole head MRI. Prof Al-Chalabi used this picture to explain the differences between upper and lower motor neurones (upper motor neurones from the brain to the spinal cord and lower motor neurones from the spinal cord to the muscles).

MND is an ‘umbrella’ term for a number of related clinical diagnoses, including ALS, PMA and PLS – the distinctions are made by whether upper or lower motor neurones are affected. However, if you feed lots of data about people with all types of MND into a computer, it comes up with a different group of categories of MND – so there must be more to the causes of this disease than meets the eye. So going back to the title of his presentation are they nature, nurture, genetics or chance?

To look at these questions as a whole Prof Al-Chalabi used an analogy of the great fire of London. The first thing that he commented on was that some buildings were vulnerable to the fire (wooden ones) and some weren’t (those made of stone, with walls around them). The chance element was that the fire start in the east and spread west – due to a gale that day – the direction of the wind is generally in the other direction.

In MND, the chance finding is the hardest to investigate – if we can’t explain it, we’ll explain it by chance! The next section of his talk he gave an overview of some of the many factors that researchers have investigated into looking at the ‘nurture’ aspects of developing MND (a field of research known as epidemiology). Looking at the age that people develop MND, whether there are ‘hotspots’ of areas where people are more likely to develop the disease, links between physical activity and smoking; he said that it was hard to draw conclusions, saying that smoking might be a ‘pre-risk’ factor and the link between MND and physical activity is still being investigated.

The last part of the talk was looking at the genetic component as to why people might develop MND, giving an overview of the latest disease-causing (or primary gene mutations) and risk factor genes that have been found to date. Using illustrations of real-time animations from the Howard Hughes Medical Institute Prof Al-Chalabi described some of the broad categories the gene defects fall into: RNA processing, protein re-cycling system (the proteasome) and those linked to the internal skeleton on the cell (the cytoskeleton).

Perhaps not suprizingly, he concluded that of nature, nurture or genetics as the cause of MND “overall, all these factors play a part, it’s impossible to separate them”.

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 

Share nicely!

The phrase ‘Share nicely’ is one that I associate with children sharing their toys, sweets and perhaps even Wii time. However, it works well in a research context too. A steady momentum has been building of new ways to share, so I wanted to write a post to highlight them.

For the last 23 years the MND Association has been encouraging researchers around the world to swop results, tips on how lab experiments work best and share ideas, at the International Symposium on ALS/MND . They might also share email addresses, phone numbers and who knows, even Twitter usernames too!  This three day conference is organised by us every year, hosted in a different city around the world. It is the largest medical and scientific conference on MND and the premier event in the MND research calendar, attracting over 800 delegates, representing the energy and dynamism of the global MND research community.

A key part of preparing for the International Symposium is the production of the conference abstract book. As Sam explained in her post in August , the abstract book is essentially the conference ‘catalogue’ or guide. It contains a summary of each presentation that will be made in Chicago next month – over 90 talks and hundreds of ‘poster’ presentations are listed. Alongside the science, the lists of the researchers involved are included too.

 Last year, this catalogue was included in the conference delegate packs when they arrived at the meeting, and the same week the abstracts were posted on the MND Association’s website (they are still there!).

You can read the Symposium summaries now!

But this year we’ve done things differently. The first thing that we’ve done is make the abstract book (the catalogue) available online a MONTH before the conference. The full text of the abstract book has been available since Monday, 5 November. The second big thing is that they are available to access for free from the ‘ALS’ journal website. We hope that more researchers will find them here, rather than on the MND Association’s website (where they’ve been before). Making these abstracts more widely available is part of a broader push by research funding bodies and policy makers to make the most of scientific data and information –a movement known as ‘open access’.

Symposium abstracts available online now

Open access – read the research results now, and for free

Away from the conference room, a standard way that researchers make their results known to their peers, and the world in general, is to write up their experiments in a research paper. Papers are reviewed by those working in a similar area, before they are accepted for publication. (If you want to know more about this process, there’s a great explanation on the Sense about Science ‘s publication ‘I don’t know what to believe’ ).

Publication where? you might be asking – here’s where the debate begins! Most scientific papers are published in research journals where either individual researchers, or their libraries pay to be able to read the article in full. So, if you or your library doesn’t pay, you can’t read it! The approach preferred by the open access movement is that the researchers pay a fee to publish their work, then anyone can read it for free as soon as it is published. The costs of paying to have your research paper published ‘open access’ typically represents approximately 1% of the costs of conducting the research in the first place.

At the MND Association, we believe that by mandating our grantees to publish their results open access a greater number of people will read them – moving us faster towards our goal of a world free of MND (more info on our open access policy here).

Over the last year, this topic has been discussed more broadly – when the government announced its commitment to open access in the summer it made newspaper front pages! More and more organisations are signing up to open access publishing – last week an online database for finding research papers re-named itself from ‘UK PubMed Central’ to ‘Europe PubMed Central’ (http://europepmc.org/ ), reflecting the broader commitment to sharing research results in this way.

Catch the Chicago buzz!

An easier way to enjoy the buzz of the International Symposium on ALS/MND is to read the reports from the meeting on this blog, rather than read the full summaries available open access. We are already looking at which topics we’d like to report on, avoiding the scientific jargon where-ever we can. Let us be ‘Q’ to your James Bond!

Preparing for the windy city: Symposium update

Every year we are responsible, as an Association, for organising the BIGGEST international conference event of the year on MND. The 23rd International Symposium on ALS/MND will return, after 16 years, to the windy city of Chicago from the 5-7 December this year.

This event is one of the most exciting events in the research calendar for those involved in MND research, and it promises to be full to the brim with exciting, cutting edge presentations. Scientists, clinicians and health care professionals across the globe come together every year for this stimulating event.

The deadline for abstract submission was back in May and we’ve been incredibly busy since then in compiling the abstracts for this year’s Symposium.

This year we received 419 high quality abstracts from across the globe, totalling 172,581 words! The Symposium Programme Committee, chaired by Prof. Wim Robberecht, had to review every single one of these in order to compile a stimulating and varied programme.

This year the Symposium will consist of a total of 96 oral presentations, with joint opening and closing plenary sessions on risk factors of the disease and the challenges of translating knowledge to treatment. There will be parallel scientific and clinical sessions exploring a wide variety of topics from target pathways, disease models and biomarkers, through to cognitive changes, multidisciplinary management and clinical trials. The final programme offers plenty of new ideas and key insights, particularly into the newly discovered C9ORF72 gene.

The Symposium will also see 251 poster presentations, and 55 work in progress poster presentations, showcased on a wide range of scientific and clinical themes that all sound incredibly interesting!

Me and Kelly have spent the past several weeks editing, formatting, proof reading and compiling all of these abstracts, which were sent to the publisher last week. The final document was 290 pages long and consisted of 150,096 words! The next stages of this process for us are to receive the proofs back from the publisher so that we can double, and triple, check them before they are ready for the Symposium. We will also be letting authors know their final poster numbers and timings so that they can get their presentations in order for the big event.

The full Program is available NOW on our website to give you an insight into the themes, and topics, that will be presented this year http://www.mndassociation.org/research/International+Symposium/Programme