Symposium LIVE

Perth (Pe)

Organised by the MND Association, the International Symposium on ALS/MND is the largest medical and scientific conference specific to MND/ALS in the world. Held annually at venues around the world, this year’s 30th Symposium sees us returning to Australia on 4-6 December 2019. This time, in the city of Perth.

Each Symposium is hosted by an ALS/MND Association from the home country, and this year’s hosts are MND Australia, the leading charity in Australia providing care and support to people affected by MND, as well as funding vital research into finding a cure. They will be hosting in partnership with MNDAWA (MND of Western Australia).

Combining big-city attractions with relaxed, informal surroundings, Perth has everything you need for an unforgettable visit. It boasts exciting architecture, inspiring museums and galleries, a diverse selection of shops, an abundance of restaurants and bars, a vibrant entertainment scene and wonderful open spaces.

Find out more about Perth – including what to do if you’re interested in exploring the city either before, after or during the conference.

MND Australia & MNDAWA (Au)

MND Australia will be hosting the 30th International Symposium on MND/ALS this year in partnership with MNDAWA (Motor Neurone Disease Association of Western Australia).

MND Australia is a non-profit organisation that is the national voice representing all Australians who share the vision of a world without MND. Drawing on 35 years of experience, MND Australia works with a national network of State MND Associations to advocate, educate and raise awareness. Their goal is to empower Australians impacted by MND to live better for longer. Until there is a cure, MND Australia’s research arm, the MND Research Institute of Australia, will promote and fund the best research with the greatest chance of making MND treatable.

MNDAWA is a non-profit organisation that is the specialist support organisation in Western Australia. It is committed to working with people living with MND, their carers and families, ensuring they will not be alone.

Global Walk to D’feet MND (Gw)

All delegates attending the International Symposium on ALS/MND and the International Alliance meetings are invited to the inaugural Global Walk to D’Feet MND in Perth to raise awareness of ALS/MND.

After the first day of the Symposium, on Wednesday 4 December at 18:15, we will be taking a 5 km walk (wheelchair-accessible) along Perth’s picturesque Swan River. We will be meeting at the carousel in Elizabeth Quay at 18:00.

Following the walk, Cytokinetics warmly invites all delegates who take part in the walk to join them as they honour and recognise the contributions of advocacy groups worldwide. Local Australian barbecue food and refreshments will be served in the Summer Garden at the Perth Convention and Exhibition Centre from 19:00.

If you’re coming along, please wear a t-shirt representing your country’s ALS/MND association or your institution (MNDA Western Australia t-shirts will be available to purchase on the day). Also, please remember to wear a hat (it’s summer in Perth!) and comfortable walking shoes.

Awards (Aw)

Various awards will be presented in the opening session of the 30^th International Symposium in Perth this year, including the following:

The International Alliance Humanitarian Award is given annually to recognise an individual or groups whose work has made a contribution of international significance to people affected by ALS/MND. Last year at our 29th International Symposium in Glasgow, the prestigious honour was awarded to our own Director of Research Development, Dr Brian Dickie, in recognition of his tireless work in progressing research into MND over the past 22 years.

At the Allied Professionals Forum before the Symposium, the Allied Health Professional Award is presented by the International Alliance of ALS/MND Associations to recognise an individual committed to providing exceptional care to people with ALS/MND. The recipient of this year’s award is Rachael Marsden from Oxford MND Care Centre. Rachael couldn’t be at the APF today because she’s part of the TandemWOW riding around the world to raise money for MND Assoc. Professor Martin Turner accepted the award on behalf of Rachael, who dedicated the award to her mother.

Paulo Gontijo Award – Established in 2007, the Paulo Gontijo Award recognises young researchers below 40 years of age who have dedicated their scientific work to investigate the causes and treatment of motor neuron disease. The award was judged rigorously by the jury committee of the Paulo Gontijo Institute (IPG), composed of five researchers recognised by the international scientific community. This year, the 11^th PG Award internationally recognises another UK MND scientist – Dr Laura Ferraiuolo, from the Sheffield Institute of Translational Neuroscience (SITraN), for her investigation into the role of astrocyte-secreted extravesicular vesicles as well as for her continuous dedication to understand and find a treatment for MND. Dr Ferraiuolo will present the findings of her winning paper at the International Symposium in Perth this December.

The first annual Healey Center Award for Innovation will be announced this year during the joint closing session of the Symposium. This award will be the first to recognize exceptional achievements for an individual or team in scientific advances in ALS from around the world.

Satellite meetings (Sm)

Whilst the main Symposium runs over three days, Wednesday to Friday, there are also several satellite meetings in the days before as well as during the Symposium itself. The International Alliance of ALS/MND Associations organises meetings to serve the broader ALS/MND community: The Annual International Alliance Meeting, on the 1-2 December 2019 and Allied Professionals Forum on the 3 December.

The Annual Alliance Meeting is attended by representatives of ALS/MND associations from around the world and provides the opportunity for these associations to meet and share knowledge of supporting people living with ALS/MND. It is also an opportunity for representatives from around the world to discuss developments and planning from their organisations, patient care and funding, and the role and activities of the Alliance and its Board of Directors.  View the 2019 agenda here.

The Allied Professionals Forum (APF) is for healthcare professionals, such as physiotherapists, nutritionists, speech-language therapists and more, who specialise in ALS/MND. It is an educational and training forum and offers healthcare professionals from around the world an opportunity to share ideas about good practice in the daily care management of people living with ALS/MND.

During the Symposium there is also a number of smaller meetings covering several subject areas that delegates can attend, encouraging further knowledge sharing and collaborations. The list of 2019 satellite meetings is now available.

ALS/MND Connect (Co)

Every year the International Alliance of MND/ALS Associations invite the host association to organise a free ‘ALS/MND Connect‘ session (formerly called Ask the Experts), as an addendum to the Alliance meeting. It is designed specifically for people living with MND and their caregivers to attend an afternoon of presentations by neurologists and researchers, then participate in a ‘question and answer’ session afterwards.

This year the event takes place on Monday 2 December 2019 from 2-4.30pm (GMT+8) at the Perth Convention and Exhibition Centre, meeting rooms 1 and 2.

This year, we will hear from Professor Matthew Kiernan AM  (The University of Sydney, Australia), Professor Ammar Al Chalabi (King’s MND Care and Research Centre, United Kingdom), and Professor Leonard Van den Berg (University Medical Center Utrecht, Netherlands). View the 2019 agenda here.

The session is also live streamed on Facebook, so anyone from around the world can attend and ask questions online – bit.ly/2OjmFrv

There is no need to register for the ALS/MND Connect session – it is free of charge for all attendees, whether in-person or online!

People with MND (Pw)

People living with MND, their carers and families are at the heart of everything we do, and our reason for organising the Symposium every year. Whilst the event is aimed primarily at scientists and healthcare professionals, there is an opportunity for people with MND to attend, via the Patient Fellows Programme managed by the ALS Therapeutic Development Institute (ALSTDI). This allows some people with MND to be funded to attend the Symposium and then share their experiences via an article or social media.

In July this year, we supported a one-day event called MND Engage at the Francis Crick Institute in London. The event was organised by researchers from the Francis Crick Institute in London to bring several UK-based MND researchers together with people affected by MND to explore ways in which public engagement in MND research could be improved.

The aim of the day was to collaboratively produce a short, engaging and informative video that provided an answer to an MND research question and was an opportunity for researchers to understand the challenges and importance of explaining MND research in an understandable way for a public audience. To see some of the videos produced, please visit the YouTube MND Engage channel. Vote for your favourite video with a like!

Poster presentations (Po)

Researchers who would like to present at the Symposium must submit an abstract – an overview of their research and findings. A Programme Committee then decides who will be given the chance to present to an audience from the stage (oral presentations) and who will be offered a poster – the chance to display their work in the form of a poster at a dedicated session. Some submissions do not get offered either.

This year, as well as having 110 speakers, we also have over 420 poster presentations. Giving researchers the opportunity to talk about their work with the wider MND research community with a poster, means that even more exciting and innovative work can be shared than would be possible with just oral presentations. The poster sessions encourage networking and collaboration, bringing together researchers, clinicians, neurologists and other healthcare professionals. The poster sessions also give researchers who are still in the early stages of their work, and don’t yet have any results, to present in the Work in Progress section.

You can read all the abstracts online. Where we have mentioned a specific poster in a tile on the periodic table, we have included the code for that poster, for example RNM-03. This tells you that the abstract for that poster can be found in the Respiratory and Nutrition Management section and it is abstract number three.

Platform presenters (Pp)

Researchers who would like to present at the Symposium must submit an abstract – an overview of their research and findings. A Programme Committee then decides who will be given the chance to present to an audience from the stage – platform presentations and who will be offered a poster – the chance to display their work in the form of a poster at a dedicated session. Some submissions do not get offered either.

Platform presentations are prestigious, and Perth will hear 110 speakers over the three days of the Symposium. These talks will be split between three sessions; biomedical (A), clinical (B), and alternative mixed (C). Each session is organised by specific themes such as genetics, clinical trials or neuroimaging. See the full programme for this year’s Symposium.

Alongside these presentations we also invite several plenary (keynote) speakers who are the world experts in their respective fields. Their talks complement the Symposium sessions by providing an overview of a variety of topics across the ALS/MND research and clinical management spectrum. See this year’s plenary speakers.

You can read all the accepted abstracts online. Please note, the page may take a couple of minutes to load. All platform presentations have a code beginning with ‘C’ followed by a number (e.g. C50). This will help you locate the specific abstract mentioned throughout the periodic table topics.

Plenary speakers (Pl)

Every year we invite a number of plenary speakers who are experts in their respective fields. Their talks complement the Symposium sessions by providing a coherent overview on a variety of topics across the ALS/MND research and clinical management spectrum.

This year’s plenary speakers are:

• Dr Jeffrey J Iliff – University of Washington School of Medicine (USA)
  ‘Glymphatic system dysfunction as a driver of protein mis-aggregation in neurodegenerative disease’
  Session 1: Joint Opening Session (C1)
• Professor Martin Turner – University of Oxford (UK)
  ‘The biomarker challenge: What is it, and are we there yet?’
  Session 1: Joint Opening Session (C2)
• Professor Justin Yerbury – University of Wollongong (Australia)
  ‘The fine balance of proteostasis and its implications for ALS
  Session 2A: Proteostasis/Proteotoxicity (C3)
  (You can read about Prof Yerbury’s work in this blog article)
• Associate Professor Kenneth Rodgers – University of Technology Sydney (Australia)
  ‘Non-protein amino acids and neurodegenerative disease’
  Session 2A: Proteostasis/Proteotoxicity (C7)
• Dr Hiroshi Nishimune – University of Kansas School of Medicine (USA)
  ‘Neuromuscular degeneration in ALS and SMA’
  Session 3A: Synaptic Pathology (C19)
• Professor Nortina Shahrizaila – University of Malaya
  ‘ALS phenotypes, demographics and clinical management in Asia’
  Session 3B: Demographics and clinical features (C23)
• Professor Naomi Wray – University of Queensland (Australia)
  ‘Future direction in ALS genomics’
  Session 3C: Genomics (C27)
• Professor Don W Cleveland – University of California, San Diego (USA)
  ‘Designer drug therapy for human neurodegenerative disease’
  Session 4A: Therapeutic Strategies (C32)
• Professor Steven Finkbeiner – the J David Gladstone Institutes and University of California (San Francisco (USA)
  ‘iPSC-derived models for genetic and compound screening in ALS’
  Session 4A: Therapeutic Strategies (C33)
• Professor Erik P Pioro – Section of ALS & Related Disorders Cleveland Clinic (USA)
  ‘Pseudobulbar effect in ALS: Not (only) a laughing matter
  Session 4B: Non-motor Symptoms (C37)
• Professor Samar Aoun – Perron Institute for Neurological and Translational Science and La Trobe University (Australia)
  ‘Supporting MND family carers from diagnosis to bereavement: The palliative approach to care’
  Session 5B: Carer and Family Support (C52)
• Dr Melinda S Kavanaugh – University of Wisconsin – Milwaukee (USA)
  ‘Research and support for young caregivers in families with ALS’
  Session 5B: Carer and Family Support (C53)
• Dr Gen Sobue – Nagoya University Graduate School of Medicine (Japan)
  ‘Lessons from SBMA study: Pathophysiology, clinical characteristics and treatment strategies’
  Session 5C: The Spectrum of Motor Neuron Disorders (C56)
• Professor Shigeki Kuzuhara – Suzuka University of Medical Science (Japan)
  ‘ALS-PDC of the Kii Peninsula, Japan: Clinical and neuropathological features and epidemiology’
  Session 5C: The Spectrum of Motor Neuron Disorders (C57)
• Dr Arindra Nath – National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda, Maryland (USA)
  ‘Investigating the role of endogenous retroviruses in ALS’
  Session 6A: Human Cell Biology and Pathology (C60)
• Professor Luc Deliens – Ghent University and Vrije Universiteit Brussel (Belgium)
  ‘Palliative care and healthcare utilisation at the end of life in people with ALS’
  Session 6B: Palliative Care (C65)
• Dr Julian Grosskreutz – University Hospital Jena (Germany)
  ‘Is ALS a network disease?’
  Session 6C: Neuroimaging (C68)
• Dr Susan E Mathers – Calvary Health Care Bethlehem (Australia)
  ‘Progressive neurological diseases: Modelling care’
  Session 7B: Improving Care Practice (C77)
• Associate Professor Bradley Turner – University of Melbourne (Australia)
  ‘Mouse models of ALS: Past, present and future’
  Session 8A: Disease Models (C90)
• Professor Capucine Morélot-Panzini – Pitié-Salpétrière University Hospital–Sorbonne University (France)
  ‘The multidimensional nature of respiratory failure in ALS’
  Session 9B: Respiratory Support (C105)
• Professor David J Berlowitz – University of Melbourne (Australia)
  ‘The management of disordered breathing in MND’
  Session 9B: Respiratory Support (C106)
• Associate Professor Thomas J Oxley – University of Melbourne (Australia)
  ‘The dawn of brain computer interfaces’
  Session 10: Joint Closing Session (C110)

Healthcare professionals (Hp)

As well as researchers, many healthcare professionals attend the Symposium to help expand their existing knowledge of MND. All fields are represented at the Symposium from respiratory experts to physiotherapists. It is a chance for them to hear innovative talks from experts in their field from nutritional support to quality of life and learn about new techniques and ways to improve their practice.

Helping to educate healthcare professionals is a priority for the MND Association as this will help those affected by MND have a better multi-disciplinary care plan, as well as improving their quality of life. As part of this education the Association runs conferences, study days and online learning for professionals on a range of topics. Find out more about these events for healthcare professionals.

Neuromuscular junction (Nj)

The neuromuscular junction (NMJ) is a chemical synapse formed by the contact between a motor neuron and a muscle fibre. It is at the NMJ that a motor neuron can transmit a signal to the muscle fibre, causing muscle contraction. Muscles require innervation (literally meaning ‘to put nerves into’, so when nerves go into muscle fibre, they innervate that muscle) to function and even just to maintain muscle tone to avoid the muscle from wasting away. In the NMJ nerves from the central nervous system and peripheral nervous system are linked and work together with muscles. Motor neurons release a neurotransmitter called acetylcholine which crosses the synapse at the NMJ and binds to receptors on the muscle fibre which results in a muscle contraction.

Studies have revealed the important involvement of muscles and NMJs in the initial stages of MND. But where does motor neuron degeneration begin? Both ‘dying-forward’ (where the motor neurons degenerate by glutamate excitotoxicity) or ‘dying-back’ (in which motor neuron degeneration starts at the NMJ and progresses toward the cell body) processes have been suggested and it is possible that both processes occur independently of each other. Regardless, it is acknowledged that degeneration to the NMJ, leading to skeletal muscle wasting, is a key point in MND clinical symptom onset and disease progression.

Mitochondria (Mt)

Mitochondria are organelles – specialised units within a cell that have a specific function – and are essential for a variety of cellular processes including providing energy for the cell (bioenergetics), calcium homeostasis – which regulates the concentration of calcium ions in the fluid outside the cell, lipid biosynthesis – the production of lipids (fats) which are the main form of stored energy in most organisms, and apoptosis – normal and controlled cell death.

Mitochondrial dysfunction is a common feature of many neurodegenerative diseases including MND. Disruption of mitochondrial structure, bioenergetics and stabilisation of calcium ions has been widely reported in people with MND and models of the disease and has been suggested to be directly involved in the development of MND.

Modelling MND (Mo)

In order to understand what goes wrong in MND, researchers need to study ‘something’ that, to all intents and purposes, mimics the biology of the disease. Ideally that ‘something’  has to be readily available, tangible, accessible, and available with a large enough number of samples so that any findings can be reproduced and confirmed.

There is currently no way to visualise all the complex interactions that happen in MND. For example, observing all of the biology of motor neurones in living people is impossible, and so researchers use models of the disease.

There are generally three types of models that are used to research MND:

• In vitro (meaning ‘in the glass’) models use isolated cells in a lab dish, with the most widely used being induced pluripotent stem cells (iPSCs). These are skin cells taken from people with MND that are transformed into stem cells – cells with the potential to turn into different types of cells, including motor neurones.
• In vivo (meaning ‘within the living’) models include testing in living organisms, with the most widely used animals being zebrafish, fruitflies, worms or mice.
• In silico (meaning “in silicon” as in silicon microchips) modelling, while not as common, is used to perform a computer simulation.

Retroviruses (Rv)

There is evidence to suggest that Human Endogenous Retroviruses (HERVs) may be involved in MND. Endogenous means ‘within the body’ and HERVs are genes that are found in our genome. Our genome contains all our genetic material, in the form of DNA, and is stored in the nucleus of all cells in our body. HERV-K has been directly linked to MND and has been found in the brain tissue of people with the disease.

For a long time, HERVs were believed to be ‘fossil viruses’ or ‘junk’ DNA, rendered inactive as they became defective or mutated as they were passed through generations over millions of years. They comprise up to 5-8% of the human genome and there is now evidence to suggest that they are not inactive.

HERVs are a type of gene called a retrotransposon which can ‘jump’ from one part of the genome to another. They contain DNA and use a ‘copy and paste’ mechanism which enables them to integrate themselves into the genome at a different place. In a process called transcription, the viral DNA sequences are converted into RNA, a short section of genetic code which, in normal cells, encodes for the proteins that make up the building blocks of our bodies. In virus-infected cells, the RNA is moved out of the nucleus into the cytoplasm. Using an enzyme called reverse transcriptase, the RNA is then ‘copied’ to make identical DNA sequences, moved back into the nucleus and ‘pasted’ back into the genome near another gene. This can cause disease if too many copies of the gene are made.

Using antiretroviral therapies, it may be possible to stop the malformed proteins being made.

Nutrition (Nu)

Eating and drinking form an emotive part of our lives, bringing us comfort and pleasure. Being nourished is not just about calories – for most of us, the enjoyment of food and flavour is incredibly important to quality of life. Knowing how to maintain this when living with MND can make a huge difference.

With MND, the way a person eats and drinks may need to be adapted to help them get the nutrition and fluids their body needs. They may experience difficulties with chewing and swallowing (see tile Sw for more information on swallowing), problems with hand and arm control, reduced mobility (making food preparation difficult) and fatigue, which can make the effort of eating and drinking tiring in itself.

Weight loss in MND is associated with faster disease progression and shorter survival and has several possible causes. These include loss of appetite, difficult in swallowing and hypermetabolism, which is an increase in the rate at which energy is burned – even though mobility may be limited, a person ‘burns off’ more calories than they consume.

Adaptations to the way a person eats and drinks may be needed to ensure they get the nutrition and fluid their body needs. Some people with MND choose to have a gastrostomy – a surgical opening through the abdomen into the stomach. This allows tube feeding – a way of passing specially prepared food and fluids straight into the stomach.

Respiration (Re)

MND can affect the way a person breathes by weakening the muscles that control breathing. Although this cannot be reversed, there are treatments that can help reduce symptoms such as disturbed sleep, fatigue and anxiety, and enable the person to breathe more effectively.

When breathing becomes weaker a machine may be used to support breathing. This is known as assisted ventilation. There are two types of assisted ventilation: non-invasive ventilation, where a machine supports breathing by boosting the intake of normal air through a mask, and tracheostomy ventilation, where a tube is inserted into the windpipe through the front of the neck, which enables a ventilator to support breathing.

The use of ventilation may not be suitable for everyone. If appropriate, it may help to relieve breathing problems but will not stop the progress of the disease.

Swallowing (Sw)

Swallowing problems, known as dysphagia, affect at least two-thirds of people with MND during their illness. This is due to a weakening of the muscles in the mouth and throat. If MND affects a person’s ability to swallow, it becomes harder for them to eat and drink. As a result, they are likely to experience dehydration and weight loss.

At the Symposium

Our platform presentations include a talk about a pilot trial to assess the feasibility and effect of swallowing exercises and diet in people with MND. Presented by Professor Victoria Flood, this work follows promising results from two trials looking at exercises for the strengthening of the expiratory muscles, and a study using a mouse model in which 20% of calories came from extra virgin olive oil, leading to increased survival rate, improved motor co-ordination and less muscle atrophy compared to controls (C97).

Physical exercise (Ph)

The stories about MND and physical activity that make it into the media feature prominent sports people who have been very active for a number of years. While this is good for raising awareness of the disease, it also raises concerns for people living with MND.

Most concerns fall into two categories: did the amount of physical activity I undertook before my diagnosis cause my MND and can I continue with physical activity after my diagnosis, or will this make my MND worse?

Physical activity ranges from gentle exercise, like walking, to more vigorous daily activity like working out at a gym, to the levels achieved by professional sportspeople and elite athletes.

Exercise is widely recommended to the general population due to its benefits to health and wellbeing. It improves the cardiovascular, respiratory, musculoskeletal, and endocrine functions and leads to psychological wellbeing. Many people with MND specifically ask whether they can safely continue to exercise regularly without fear of accelerating their disease. At present, there is no firm evidence that exercise exerts a harmful effect, although avoidance of very strenuous activity would seem to be sensible. Low-grade, managed exercise programmes may even be of benefit.

For many people with MND, exercise played an integral role in their pre-diagnosis lives. A wish to continue exercising, in the hope it will have positive effects on endurance and strength, is understandable. While pre-diagnosis exercise is likely to have involved aerobic training and strengthening programmes, research has shown that moderate exercise can slow functional decline whereas high intensity training can be detrimental.

Caregiver support (Cs)

When someone is diagnosed with MND, the changes affect not only the person with the disease but also those close to them. Becoming a carer for someone with MND can be very challenging and, over time, the level of care needed will increase – sometimes rapidly.

Supporting someone with MND can often feel emotionally overwhelming but there can be many positive emotions, such as satisfaction when a task or challenge is successfully completed, especially if this has involved both the carer and the person with MND. It is important that the carer takes time to look after their own needs, even if this feels impossible when facing the challenges of supporting someone with MND.

Palliative care (Pc)

This section talks openly about death and end of life decisions.

The aim of hospice and palliative care is to give the best possible quality of life with a life-shortening illness. For maximum benefit to people with MND, this type of care is recommended from the point of diagnosis onward.

Palliative care refers to specialised care services that focus on quality of life and symptom control when an individual has an illness that can’t be cured. This includes practical help, medication to ease symptoms and support for the individual and their family. Palliative care isn’t just for end of life. It may be given earlier in a person’s illness in conjunction with other therapies treating the condition.

Palliative care is of utmost importance in MND and focusing on managing symptoms and improving quality of life of people living with the disease is a priority of healthcare professionals. Because of the nature of the disease, it is important for those affected by MND to know about the symptoms they should expect as the disease progresses, and how best to manage them. Research is always ongoing to find out how best to manage symptoms and when to utilise life-sustaining measures.

Thinking about end of life is rarely an easy task. Some of the decisions that need to be made are very difficult and everyone’s experience will be different. People may have troubling thoughts such as ‘what will happen?’, ‘will it hurt?’ and ‘will I lose control?’. It is normal to expect heightened emotions when facing end of life decisions, but it has been reported that people feel relieved and much calmer having made their plans and knowing what is likely and less likely to happen. Every individual’s needs and preferences will be personal to them but can be influenced by those around them, leaving them feeling angry, guilty, sad and even relief. These are all normal and expected reactions to challenging circumstances. With support from health and social care professionals, and family and friends, difficult feelings usually become more manageable over time.

Cognition & behaviour (Cb)

Up to half of people with MND experience changes to how they think and behave, and these affect people in different ways. For some they will have little effect on daily life, while others will need significant day-to-day support. In a small number of cases, people with MND develop frontotemporal dementia (FTD).

People with MND may experience changes to their thinking and learning, language and communication, and behaviour and emotions. It may become more difficult for them to make and carry out plans, process information and solve problems. They may find it harder to recognise words when reading or writing, have difficulty spelling or find it hard to follow conversations. They might also begin to lack enthusiasm, find it difficult to manage emotions and behave inappropriately in social situations.

If a person is affected by FTD they will experience symptoms similar to those already described but with greater severity. With FTD, memory is not usually affected although it may appear that it is due to difficulties with concentration and taking in new information.

Augmentative & alternative comms (Ac)

Augmentative and alternative communication (AAC) tools are vital for people living with MND. As their disease progresses, they may experience slurred speech or even completely lose the ability to speak (dystharia). To ensure that people with MND can continue to have a voice in making decisions regarding their care, technology can facilitate communication when speech is impaired. AACs can be as simple as using hand gestures, facial expression and writing, but can also include using high tech devices to communicate.

At the Symposium

A comprehensive review of the literature available on AAC in MND was carried out by researchers in Brazil with the aim of identifying types of AAC and its purpose, to assess how it might be best used by people with complex communication needs (COG-14).

Genetics (Ge)

Around 5-10% of people with MND have a family history of the disease known as familial, or inherited, MND. This is caused by a mistake in the genetic code that holds the instructions for making every protein in our bodies. This mistake may be passed down from parent to child.

There are a growing number of genes which have been associated with MND. The most common of these are SOD1, TARDBP, FUS and C9ORF72. Other extremely rare causative genes have also been identified. These discoveries represent major breakthroughs because they can provide important clues as to how motor neurones are damaged in MND and may advance our understanding of all types of the disease.

At the Symposium

Lifestyle & environment (Le)

The causes of MND are still not fully understood. Around 90% of people with MND have a sporadic form of the disease – when the disease appears for no apparent reason and with no known familial link. Sporadic MND is thought be caused by a combination of genetic, environmental and lifestyle influences.

Exposure to these factors has been extensively studied. This is known as epidemiology. Epidemiological studies have identified possible links with prior exposure to mechanical and/or electrical trauma, military service, high levels of physical activity, agricultural chemicals and a variety of heavy metals. However, these are all only suspected contributory risk factors and the evidence from studies is often circumstantial or conflicting and offers no clear conclusions.

Understanding the causes and mechanisms of motor neurone degeneration is essential to the development of new treatments. Only by understanding what goes wrong in MND can scientists identify potential drug targets and other therapies.

Inflammation (In)

Although MND is not a disease of the immune system, there is evidence from studies of patients that the levels of some types of immune cells in the blood can play a role in the speed at which the disease progresses.

Neuroinflammation is commonly seen in neurodegenerative diseases, including MND, and animal studies have shown active roles of glial (support) and immune cells in the development of MND.

Neuroinflammation is an inflammatory process thought to originate primarily from central nervous system (CNS) cell types such as microglia and astrocytes. Both cells have pro- and anti-inflammatory functions meaning that they can offer protection against cell injury or can become destructive.

For example, astrocytes are key homeostatic cells (they have the ability to maintain internal stability) that play numerous supportive roles in maintaining the brain environment. In MND, astrocytes change their shape and molecular expression patterns, and are referred to as reactive or activated astrocytes. Reactive astrocytes in MND lose their beneficial functions and gain detrimental roles. In addition, interactions between motor neurons and astrocytes are impaired in MND.

Microbiome (Mi)

Recent studies have found that microbes living in our gut (microbiome) might have an effect on the rest of the body, including the immune and nervous systems. It is possible that the microbiome may be able to communicate with and affect the immune cells in the brain and spinal cord, the microglia.

Microglia have a naturally protective effect on motor neurones and the rest of the nervous system. Therefore, if the microbiome has the potential to affect the way microglia are behaving in the brain and motor neurones of people with MND (and other neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease), the microbiome could become an important treatment target.

Researchers are currently focusing on the possible differences in the gut microbes of people with MND compared to people without the disease, in order to establish the possible connection between gut microbes and MND (and other neurodegenerative diseases).

Coming soon (X)

New content coming soon!

Motor neurone disorders (Md)

It has long been debated whether ALS/MND is one disease, or whether we should look at it as a collection of multiple conditions with similar symptoms and disease mechanisms. We are observing a large amount of variation in terms of speed of disease progression, length of survival, type of onset (bulbar or limb), absence/presence of frontotemporal dementia and its degree, as well as cause of the disease (e.g. involvement of specific genes).

This is especially important when investigating the effectiveness of a new drug in clinical trials, which might not work in the same way across all MND subgroups. A good example is the drug lithium, which was found not to be effective in treating MND, until the data re-analysis found that there was an improvement in people with a specific genetic variation (UNC13A).

Delivering diagnosis (Dd)

Breaking the news of the diagnosis of MND can be challenging for most healthcare professionals. As well as this, most people affected by MND are dissatisfied with their experience. Could there be room for improvement in the practice of delivering diagnosis and policies? More integration across care sectors and a more person-centred approach to care from the beginning could be the way forward.

At the Symposium

Delivering diagnosis will especially be discussed for healthcare professionals in two talks and several poster presentations at the Symposium this year. This includes a talk on modelling care for progressive neurological diseases (C57) and a discussion on the gap between standards and actual practice of delivering diagnosis (C78).

A poster presentation within Theme 13: Clinical management and support will discuss the diagnostic experience in MND through a UK survey (CMS-04).

Progression & prognosis (Pr)

A prognosis is defined as a likely course of a medical condition. ALS/MND is a progressive and fatal neurodegenerative disease, with an average life expectancy of two to three years. However, individual prognosis can be highly variable – from weeks to decades. Several prognostic factors are known, such as site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis, and the use of riluzole and non-invasive ventilation (NIV).

While we wait for an established tissue biomarker (a signature of a biological change), measures of clinical progression are currently the standard for monitoring disease progression. The most widely used measure is the revised ALS Functional Rating Scale (ALSFRS-R), which is a 12-item clinical chart assessing patient’s functional abilities. Each item asks about specific abilities (such as speech, swallowing, dressing, or walking) and is rated on a 5-point scale from ‘0’ severe disability) to ‘4’ (normal functioning). A cumulative score gives a physician a considered view on the person’s disease status (where 48 marks means normal functioning).

Other measures focus on more specific symptoms of the disease, including motor neurone loss, reduced breathing ability, or assessment of behaviour and thinking abilities.

Biomarkers (Bi)

There is currently no diagnostic test for MND. Because of its relatively rare nature and non-specific symptoms, it is currently being diagnosed by an exclusion method, whereby clinicians must rule out a whole range of other neurological and muscular conditions before giving a diagnosis of MND.

Finding a simple and pain-free test that would make this process easier and faster, would likely increase the effectiveness of existing and emerging treatments. These tests require searching for what is called a ‘biomarker’ – a signature of a biological change occurring in a specific disease (or a group of diseases). Some biomarkers have been identified for MND and are being tested to develop them into clinical tests.

Another reason to look for biomarkers is to keep track of the progression of the disease. Researchers are now testing various measures to see how biomarkers might change as the disease progresses, and whether these differ in people with rapid progression from those with a slower progression rate. However, due to the current lack of biomarkers, other measures of functional ability are used in clinics instead. While these are informative and provide us with a good estimate of the disease progression, they are not as accurate as biological markers.

Telehealth (Te)

Telehealth, or telemedicine, involves the use of technology to allow healthcare professionals to monitor an individual’s health and deliver care remotely. For example, they could assist in the diagnosis and management of a condition. The ultimate goals of using this technology are to increase access to care for people, decrease the frequency of clinical visits and reduce clinical costs.

For people with reduced mobility, telehealth means no long commutes to short, but critical, assessments and no waiting around. From previous studies, people taking part in remote assessments expressed higher satisfaction with the overall care they were given and appreciated remaining in the comfort of their own homes. People living long distances away from services or with increasing disease related disability are usually most likely to utilise Telehealth.

Clinical trials (Ct)

Clinical trials are research studies in human volunteers that determine whether potential treatments are safe and effective. All clinical trials have strict guidelines about who can take part (factors that allow inclusion criteria). Clinical trials are usually conducted in four progressive phases which check for safety and efficacy, establish the correct dosage and method of delivery, and assess the drug’s ability to treat the condition it is designed for.

Clinical trials take many years to complete and are often extremely costly. At any stage the drug can be deemed too dangerous, or inefficient, to take into the next phase. To speed up the process, clinical trials are beginning to incorporate a biomarker element (a biological characteristic) into their design. Monitoring levels of specific biomarkers during a trial will help establish if the drug or intervention being tested is influencing disease progression.

Platform trials (Pt)

There is an urgent need for innovative clinical trial designs to accelerate the drug development process to test awaiting candidate therapies and develop new therapeutics for ALS/MND. A potential solution is an adaptive platform trial which allows multiple drugs to be tested and evaluated for each drug’s efficacy simultaneously, and with fewer participants required.

At the Symposium

The Healey Center ALS Platform Trial will energise the ALS community by doing this. As well as being able to find an effective therapy more quickly, the platform trial could drive the development of novel outcome measures and biomarkers (biological signatures of disease) and provide data for future discovery. Just recently, five “promising” candidate treatments from among 30 applications had be chosen to test in its first platform trial for ALS.

Sabrina Paganoni, MD, PhD, a faculty member at the Healey Center, will discuss the ALS Platform Trial, including its design considerations and statistical efficiencies, as a plenary talk (C8) at the Symposium in Session 2B: Clinical trials and within Theme 9 of poster presentations (CLT-05).

Gene therapy (Gt)

There are a growing number of genes which have been associated with MND. The most common of these are SOD1, TARDBP (TDP-43), FUS and C9ORF72. Other extremely rare genes have also been identified to be causative. There are currently no treatments to prevent the effects of the gene damage that is being passed from one generation to another. However, research is underway to find such treatments. An emerging innovative approach has been gene therapy.

Gene therapy is designed to introduce genetic material into cells to alter how faulty/missing genes work in order to correct genetic disorders. It is expected at the very least to alleviate the symptoms and slow the progression of MND. Hopefully, gene therapy could even prevent the disease when a faulty gene is diagnosed and treated at an early-enough stage.

Brain-computer interface (Bc)

A brain-computer interface (BCI) is a direct communication pathway between an enhanced or wired brain and an external device.

Although this is technically not considered a treatment yet, the implantation of the Stentrode®, a minimally invasive technology, BCI system in patients could have potential to restore communication in people with severe paralysis. This is similar to the procedure utilised for implantation of cardiac pacemakers. The implantable BCI device is designed to record brain activity and stream thoughts wirelessly directly from the brain.

The first clinical feasibility trial evaluating this technology recently began in September 2019, making a preliminary step on the approval pathway.

CuATSM (Cu)

Copper ATSM (CuATSM) is a small, orally administered, man-made compound that can deliver copper to cells where the cell’s energy batteries, mitochondria, have been damaged. Damaged mitochondria are considered a hallmark of several neurodegenerative disorders, including MND/ALS, Parkinson’s disease, and Alzheimer’s disease. CuATSM allows for selective delivery of the drug (i.e. to only those cells that have been damaged) and it is blood-brain barrier permeable.

It is a candidate MND drug that is being investigated for its effects of slowing down disease progression and improving respiratory and cognitive function.

Drug development is a long process that involves rigorous checks in numerous phases. Phase 1 results were first announced in December 2018 at our International Symposium in Glasgow. The treatment was observed to be safe and well-tolerated, with some beneficial effect.

Drug screening (Ds)

Before a drug can be tested in clinical trials (in humans), it first must be examined in a lab to provide an insight into its mechanism (how it is likely to work in the body), safety, and preliminary effectiveness. These studies can be done in cells in a lab dish (in vitro), in animals (in vivo), or using computer modelling (in silico).

While there is only a limited number of clinical trials, there are many compounds currently being investigated that could have the potential to be developed into ALS/MND treatments.

In general, only an extremely small proportion of compounds tested in pre-clinical studies get to the final drug approval stage, reflecting the rigorous and strict process assuring that only safe drugs of good quality are tested in clinical trials and approved.