International Symposium on ALS/MND: Destination Orlando

The August Bank holiday weekend is always greeted with a sigh of relief from the Research Development Team as it signals the sending off of the International Symposium on ALS/MND abstract book to the publishers.

The book includes teasers/previews – called abstracts – of all the talks and posters that will be presented at this year’s symposium. It is the result of many months of hard work by the team, hours of editing and proof reading, and the sending and receiving of hundreds of emails.orlando 2015 logo

But why is the symposium such a big deal and why are the MND Association involved in organising it?

The birth of the International Symposium on ALS/MND

It all started in Birmingham…

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. This was the MND Association’s reasoning behind the creation of the International Symposium on ALS/MND.

The first was held in Birmingham in 1990, and was attended by 50 MND researchers. From then on it has grown and grown, and is now a truly international event. In order to attract a wider international audience and invite local experts to speak the location changes each year. Previously it has been held in locations including Sydney, Chicago and Milan.

Last year in Brussels we had 848 people attend, showing how large the global MND research community has become. We expect a similar number of people to attend this year.Read More »

One week on – Reflections on my first experience of the International Symposium on ALS/MND

Our recent blog articles describe lots of fascinating science and the progress in the care and treatment of MND/ALS that was presented at the symposium.  Personally, another really positive aspect was the opportunity to meet some of the researchers face-to-face. This included several senior scientists and clinicians whose work we support, some of whom gave lectures or chaired sessions. The symposium also gave presentation opportunities to PhD students and post-doctoral scientists, some of whom were attending their first International Symposium. We invited several from the UK to an ‘ice-breaker’ social on the Friday evening before the main lecture sessions began. Not all were able to attend, but a good group gathered with us, getting to know each other, and we met others later as they presented their posters. 

Sheffield University was well represented, including current grantees Emily Goodall and Clare Wood-Allum who both presented posters. Newer to ALS research was Guiseppe (‘Bepe’) Battaglia part of a cross-disciplinary group of collaborators who call themselves ViNCeNS for ‘Virus-like Nanoparticles for targeting the Central Nervous System’ with a website at

‘Fishing’ for new animal models of MND

Two others at our ‘ice-breaker’ gave lectures during the Saturday session on ‘Emerging Disease Models’.   Marc Da Costa (also from Sheffield) described some outcomes of his PhD project developing a new zebrafish with a mutated SOD1 gene.  Zebrafish are popular models for neurological conditions (there was a second presentation from an US-based group), as the fish embryos are transparent, so their neurones can be studied easily under the microscope.  Their muscular strength can be judged by the amount they move (studied by automated analysis of video) or by their progress swimming against a ‘current’ in a tube.  Marc studies the differences between fish with normal or mutant SOD1.  The latter have more difficulty swimming, and are more vulnerable to stress (for example, added toxic chemicals).  Marc can test the effects of potential drugs on the stressed fish, and has already seen some promising results.

Looking in a ‘library’ for MND mice

Another new animal model was presented by Peter Joyce (MND Association funded, based at the Medical Research Council Laboratories near Oxford).  His mouse strain carries a mutation (mistake) in its native (mouse) SOD1 gene, matching one recently reported from a human family with ALS.  This is different from the more established SOD1 mouse model, in which the MND-like symptoms develop as a result of multiple copies of an added human mutant gene.  Peter is studying the timescale in which muscle problems develop, relating these to changes in the neurones.  The MRC has a huge ‘library’ of mouse mutations available, so Peter will be investigating if others match mutations reported in different ALS families, possibly looking for collaborators to work on these.

Presenting the impact of healthcare decisions

A completely different type of research was presented as posters by two researchers working with Carolyn Young at the University of Liverpool.  Hikari Ando has been studying the reasons why some people with MND decide not to accept the offer of non-invasive ventilation (NIV), and the extent to it is actually used by at home.  Chris Gibbons’ work covered the assessment of quality of life for people with MND, particularly the role of fatigue and depression. 

Final thoughts

It was particularly inspiring to meet so many UK-based researchers, filling all of us from the MND Association with more incurable optimism.  Of course we also met many other people too – the attendees, many of whom collaborate internationally, came from more than 30 countries.

Classifying MND

As the symposium draws to a close, Prof Nigel Leigh gives the final scheduled talk. Prof Leigh is an eminent researcher and clinician and is arguably one of the forefathers of MND research and care – especially in the UK. Throughout his career he has made many important discoveries, founded the first UK MND care centre and inspired many young clinicians and researchers – many of whom are now eminent researchers themselves.

In his talk, Prof Leigh discussed the classifications of MND – such as PLS, flail arm, bulbar etc, and the notion that this way of thinking is out of date. To explain this, in his abstract he poetically wrote that “just as classical notions of the constellations and galaxies tell us little about astrophysics, so the identification of phenotypes (clinical symptoms) with theory may be more fanciful than helpful”. This refers to the fact that the presentation of MND does not tell us anything about what is happening inside the body. With our growing knowledge in genetics and biomarkers for MND, this may start to change.

He finishes by calling for a new consensus on the classifications of forms of MND.

The closing session: what’s happening in Chromosome 9

 After three days of deep discussion and debate among researchers clinicians and health and social care professionals, the final talks of the symposium begin. The room fills with over 800 people for the last time.

The closing session begins with ‘late breaking news’. This is an exciting opportunity for very new and exciting results to be explained to all delegates.

Dr Bryan Traynor, who is a genetic researcher based at the National Institute for Health in Maryland, America was first to take to the stage. Last week, Dr Traynor and colleagues released their finding that a new causative gene for MND had been identified. This is the third to be discovered this year alone, which demonstrates the immense speed that MND genetic research is moving.

In the talk, Dr Traynor described his recent findings. The gene is called VCP, which stands for ‘Vallicin-Containing Protein’. It was first discovered by Bryan’s group in a family affected by inherited (familial) MND and was soon verified as a cause of the disease for other people with familial MND.

They speculate that VCP is the cause of MND for 2% of cases of familial MND. For more information on what this finding means to people affected by MND, please read our press release on our website.

Through Bryan’s talk, we also heard that this particular gene is found on chromosome 9. A chromosome is an organisational structure for our genetic code – as humans, we have 23 pairs numbered 1 to 22 with the final pair being the sex chromosomes (XX or XY). The news that VCP is on chromosome 9 is an interesting one given that earlier this year a study, led by Prof Ammar Al-Chalabi – an MND Association funded researcher, at King’s College London found a region of DNA within chromosome 9 that contains three genes that may be associated with the randomly occurring sporadic form of MND; a condition called ‘fronto-temporal dementia’ (FTD) that affects behaviour, emotional response and language skills; as well as a rare inherited form of MND called MND-FTD.

However, it is important to note that the genetic regions are not the same, they are just found on the same ‘street’ of the chromosome. An interesting co-incidence none-the-less!

Prof Ammar Al-Chalabi next took to the stage with a talk entitled: What else is hiding in Chromosome 9. In his talk he discussed the reasons why finding the exact underlying genetic cause of MND-FTD in chromosome 9 is so difficult.

Welcome to a new player in identifying a cause of MND

MND isn’t just about motor neurones going wrong in an otherwise perfectly functioning nervous system. A group of cells called glia, which surround motor neurones and normally provide them with support and nourishment, can dysfunction too. It’s likely that they even hold most of the cards when it comes to determining how MND progresses, so they’re not to be overlooked. One of the ‘Dons’ (excuse the pun…) of glial cell research in MND, Don Cleveland, opened this session with an overview of how each type of glial cell contributes to the cause of MND. He concluded this part of his talk by saying that the toxicity within different cell types come together to kill motor neurones. Work has now begun on the development of therapies utilizing what we know about these support cells, including plans for an early safety study (phase 1) of a stem cell astrocyte therapy in 2014. I know that this sounds like a long time away, but I would refer you to my post on Nicholas Boulis presentation to understand why!

With the benefits of hindsight, one the most telling questions for Professor Cleveland was what about the role of oligodendrocytes in MND – which are a type of brain cell. He replied that the answer to this would be clear by the end of the session – and it certainly was! An animated and excited Professor Rothstein got up to speak a few talks later. The statements on his opening slide said it all: “ALS is a disorder of oligodendroglial cells” and “Oligodendrocytes are a dominant neuronal support”. It was a whistle-stop tour through a lot of different types of experiments. Perhaps the most striking of these was the study where removing damaged SOD1 proteins from oligodendrocytes increased the survival by 126 days in SOD1 mice. He concluded that there was still an enormous amount to do to understand the role of these cells.

This session gave Laura Ferraiuolo, a young MND researcher whose career was kick-started by an Association-funded PhD, a chance to showcase her most recent work. During her PhD, Laura learned how to use a cutting edge technique that allows detailed analysis of subtle changes in the genetic code and how it is being ‘interpreted’ by motor neurones. During her presentation today, Laura explained how she has now applied this technique to astrocytes, a type of nerve support cell, and provided the audience with some insight into possible astrocyte-related disease mechanisms. Laura is the embodiment of what the Association’s PhD studentship programme aims to achieve – to draw promising young scientists into a productive career in MND research.

Clinical trials – design and results

This year, two sessions are related to clinical trials. The first, concerns the planning and design of clinical trials. The second is the results of recent trials.

But why should we talk about the planning of trials? Planning is a vital step if we are to find a new treatment for MND. By taking the time and effort to carefully plan trials in new and novel ways, clinical trials can be cheaper and test the true effectiveness of the treatment in a short amount of time with less people involved. By learning from other clinical trials that are currently being planned, as well as the results from trials that had a novel design, researchers can refine the way that trials are planned to speed up the process of moving potentially beneficial drugs from the laboratory to the clinic.

The first talk in the design clinical trials session talked about Phase II clinical trials. Phase II clinical trials are designed to test a number of issues regarding the treatment, including, the safety, tolerability, finding out the ‘right’ dose for it to be effective as well as a number of other issues. Due to the ever expanding list of possible issues to resolve through a Phase II clinical trial, there is no single clinical trial design that can answer every question. This presents clinical trial designers with a dilemma as Phase II trials for MND are often longer and larger than desired or possible – this leads to problems in the design and conduct of later trials.

Getting it right is certainly not an easy task, which is why it is vital that clinical trial designers learn from previous trials and constantly improve how clinical trials are conducted.

The second session provided answers to whether recent treatments that have completed clinical trials are safe or effective.

The results of recent trials for Talampanel and Pioglitazone were discussed. As a summary: Talampanel was found to be safe but not effective; Pioglitazone was found to be potentially unsafe and also did not show effectiveness in altering disease progression.

Although this is disappointing news, by sharing their results with others means that researchers can learn about the design and enrolment of clinical trials in the hope that future trials can learn from the past. Even negative trial results are an answer as to whether a treatment strategy is appropriate and should be further investigated from a different angle.

The last talk of the clinical trials session was regarding a recently completed early safety clinical trial for a new drug (named CK2017357) developed by a pharmaceutical company called Cytokinetics. In the study 67 people with MND took a single dose of either a placebo (dummy drug), small dose, or large dose of the drug on three different days. Neither the patient nor the doctors knew what they were receiving on what day.

This is an extremely novel way to approach a clinical trial, as a direct comparison of safety and preliminary effectiveness can be measured in the same person.

Through the Phase II clinical trial, they identified that within six hours of taking the drug, people had increased muscle strength and endurance which was responsive to the dose given. The drug was also found to be safe. This is positive news, but should be taken with a ‘pinch of salt’, as a much larger future clinical trial using multiple doses is needed to determine the true effectiveness of this drug.

Inspired by viruses

I attended a fantastic talk this morning in the session on ‘Translational Strategies’. This session is all about moving laboratory ideas for new treatments for MND into the clinic to test them in clinical trials.

The first talk was given by Battaglia, based at the University of Sheffield. In this presentation, he described a multidisciplinary project to develop synthetic ‘nanoparticles’ which could be used to deliver future therapies to the brain and spinal cord – and even eventually into motor neurones and support cells. This project really does take collaboration to a new level by combining the expertise of physicists, chemists and biologists and taking inspiration from the ways in which viruses have evolved to get into our cells.

In the second presentation, we heard how a small company in California (iPierian) are taking cells from patients with ALS and developing them into stem cell-like cells called ‘induced pleuripotent stem cells and then turning them into motor neurones. Their next aim is to test new compounds on these cells to test for their effectiveness in a human cellular model of MND in the hunt for new and better treatments for MND.

Carer needs, supporting diagnosis and debating physician assisted suicide

Carers play a vital role in the lives of people living with MND, so important in fact that at this year’s symposium a session addressed the fact that the needs of carers are not being met. A memorable quote for Kevin and Jane, two of our regional care development advisers, which they found pertinent was: “the forgotten patient is the caregiver” which was said by R Stutzki from Switzerland.

Jane then commented that as an Association, we are beginning to look at the needs of caregivers and that we must continue to highlight this as an important issue to health and social care professionals in the UK.

Mary O’Brien from the UK then spoke about her experiences from 20 years ago when somebody who was recently diagnosed told her: “I got my diagnosis and my future was taken away”. Both Kevin and Jane then reflected on this quote using their own experiences. In the past few decades, support for diagnosis has dramatically changed around the world. One quote that Kevin finds particularly pertinent from his time at the Association was when somebody living with MND said that their diagnosis was like “falling into a black hole”, but with help from the MND Association, this view has changed over the years.

MND is a devastating diagnosis, but with the right support in place, the diagnosis is now not the ‘black hole’ that it used to be.

This was echoed in the opening session by Robert Miller, in that over the past few decades, a deeper understanding of how to better support people living with MND has progressed. This is obviously not the end of our journey to improve diagnosis, but we are moving in the right direction.

Another talk that Jane and Kevin found interesting was one that looked at the Oregon Death with Dignity Act. Through this act, it is legal for physician assisted suicide for people with a terminal illness. In the session, both sides of the debate were discussed and the presentation then explained how evidence from a recent study revealed that of every 100 people who wanted to speak to a health and social care professional about physician assisted suicide, only ten people ordered the drug and only one person took it to end their life. L Ganzini who led the talk said that the study had shown that the main reason why people wanted to order the drug was so that they would have greater control. Ganzini then went on to explain that because most of the people who wanted to speak about physician assisted suicide received excellent hospice and palliative care, then this high quality level of care played a major role in influencing their decision. This discussion highlighted to delegates that this sensitive issue is not pertinent to just one country.

Handedness linked to symptom onset – Lessons from a poster presentation

Prof Georg Haase and Prof Peter Andersen at the poster session

This year, nearly 300 posters are being presented at the symposium – that’s three times the number of presentations being given as talks! Due to the large numbers and feedback from last year’s symposium this year we decided to split the session in two with one session on Saturday and another on Sunday.

This is the first time that the poster session has been split in two, giving delegates a longer opportunity to discuss work with the authors on a one-to-one level. It’s also often a good opportunity for young researchers to develop their presentation skills which is vital for an upcoming researcher! Hopefully given the new format, delegates will be able to share more knowledge, meet potential collaborators and come away with new information to use in their research or to ignite a new idea. The poster room was soon filled with a swarm of delegates, moving from poster to poster in search of knowledge. With over 800 delegates attending this year’s symposium, it’s no wonder that the room was humming with conversation.

One poster that was particularly interesting was that of Dr Clare Wood-Allum. The story of this work started earlier this year with an article on limb dominance (aka handedness) by Dr Martin Turner, and colleagues.

The theory for both pieces of work is that if physical exercise does increase the risk of somebody developing MND, then a person’s handedness may influence the site of onset due to the motor neurones in the handed arm being used more so than the other arm. However, due to people using both feet (generally) equally while standing etc then there would not be a relationship between footedness and side of onset.

To find out if this was true or not, Dr Turner and colleagues used to ask 343 people living with limb onset ALS to complete a questionnaire regarding their site of onset and dominant hand and foot. From their results, they identified that there was a link between the side of onset for people who had upper limb onset MND and their handedness. People with a lower limb onset did not have a relationship between their footedness and side of onset as expected.

In order for the work of Dr Turner and colleagues to be backed up, further investigative work was needed by an independent research group.

This is where Dr Wood-Allum and colleagues come in! By using case notes from 722 people with MND, they identified that in upper limb onset MND, symptoms were most likely to begin in the dominant arm. As predicted, they did not find any relationship between lower-limb onset MND and side of onset.

These two results together present a previously unrecognised feature of MND.

Studying the risk of developing MND

A very natural response to receiving a diagnosis of MND is to ask ‘Why me?’. Many people with the disease question whether their MND could have been caused by something in their environment, their occupation or a lifestyle factor such as smoking, diet or exercise.

The study of environmental and lifestyle factors that may predispose people to disease is known as epidemiology. Sporadic MND is thought to result from the cumulative effects of numerous risk factors, in people whose overall genetic make-up makes their motor neurones particularly vulnerable to damage. The identification of these risk factors could provide insight into the abnormal mechanisms underlying the development of the disease and eventually aid in disease prevention.

The trouble is, identifying these factors with any certainty is extremely difficult. In this session’s opening presentation, Ettore Beghi from Milan discussed why studies that aim to assess environmental and lifestyle contributors consistently fail to generate conclusive evidence. For instance, studies on heavy metal exposure, diet, head trauma and statin use were concluded as not having enough reliable evidence to suggest a possible risk. He did however note, that it is unlikely that statin use increases the risk of somebody developing MND as he said that “despite a 10 fold increase in statin use (in recent years), there has not been the same pattern for cases of ALS”.

He also suggested that researchers need to bear certain key considerations in mind when designing epidemiological studies, including how they select their study participants and how they should be unbias when defining the risk factors themselves.

The remaining talks in this session gave examples of how registers of people with MND in a particular country or region can be used to glean information about various aspects of the disease.

Marc Huisman described how a register of people with MND in the Netherlands has allowed him and his colleagues to investigate possible occupational risk factors. To date, these include an increased risk for farmers and electricians. They also identified (in smaller numbers and so this evidence is less reliable) that dental assistants have an increased risk, whereas general managers have a decreased risk. Their next steps are to ascertain what underlying exposures may be linked to these jobs to increase, or decrease the risk of somebody developing MND. The Dutch register also suggested that a family history of other neurodegenerative diseases may increase risk of MND, while a family history of cardiovascular disease may reduce risk.

There are still a number of questions regarding lifestyle and environmental causes that need to be answered. But, if researchers can collect reliable evidence, then the research community will be in a better position to start asking why (instead of what) particular risk factors can contribute to the cause of MND.