The global MND research community is once again preparing for one of the most anticipated events of the year—the 36th International Symposium on ALS/MND. This annual gathering is the largest scientific and medical conference dedicated solely to ALS/MND, offering an international platform to share work, exchange ideas, and spark new collaborations. Throughout November, we’ll be publishing a series of blog posts to highlight some of the exciting research being presented at this year’s Symposium.
Every year, the International Symposium on ALS/MND features a lineup of plenary speakers who are leading experts in their fields. This year, we’re excited to welcome 23 plenary speakers, each bringing their unique expertise to the global stage. Over the coming weeks, we’ll be shining a spotlight on each of these speakers and offering a glimpse into what they’ll be discussing at the Symposium.
This year, the Symposium will be held in San Diego, USA, from 5–7 December, with a virtual attendance option available. Virtual delegates will be able to join select sessions live and access all sessions on demand after the event—just like in-person attendees. We’re proud to once again bring this important event to the community and look forward to welcoming researchers, healthcare professionals and people from the wider MND community. Haven’t registered yet? There’s still time!
Our DNA contains genes, which are the instructions to make proteins, and proteins are the building blocks of our cells. Changes to the instructions in genes can affect not only what proteins are made, but how proteins are made. Understanding the changes in genes and proteins that are linked to MND can help us to understand what goes wrong in MND and why. In this blog, we will introduce some of the research talks from plenary speakers that focus on learning more about genes and proteins in MND, and how this can open up new opportunities for therapeutic intervention.
Day 1, Session 2B: Genes and Phenotypes
Studying MND in Latin American populations
MND is thought to be caused by a combination of genetic, lifestyle and environmental factors. In different parts of the world, people have different genetic backgrounds and are exposed to different environmental and lifestyle risk factors for MND. Therefore, the number of people who develop MND is varied between different groups of people around the world. To date, most of our understanding of MND has been gathered from studying people with MND in European and North American populations. However, exploring more diverse populations can reveal new insights into MND, including disease processes and potential therapeutic targets.
Dr Jose Matamala and Dr Marcondes Franca Jr, who are based at universities in Chile and Brazil, respectively, will present an overview on MND in Latin America.. In Latin America, the rate of new cases of MND is lower than in the US and Europe, but the average age of disease onset is also lower. The number of people with common genetic changes linked to MND, such as C9orf72 repeat expansions, which is the most common form of genetic-linked MND, is much lower in Latin American populations. In contrast, the frequency of much rarer genetic changes linked to MND is much higher.
Drs Matamala and Franca will discuss the importance of carrying out research in diverse populations of people with MND, in order to learn as much as possible about the disease. They will also discuss the challenges associated with studying MND in Latin America, including issues such as unequal healthcare access, a shortage of neurologists and under-resourced healthcare. By investing in MND research in underexplored populations, not only will this improve the quality of life for people living with MND in these areas, but it will also contribute more widely to the understanding of MND and potentially highlight new ways of treating MND.
Day 2, Session 5A: Epigenetics, Aging and Selective Vulnerability
Exploring how genes are switched on and off in MND
Genes need to be turned ‘on’ so that they can be made into proteins. Epigenetic studies are research projects that explore the different ways that genes are turned on and off, without changing the DNA. These controls are called epigenetic mechanisms, and just like disease-linked changes to DNA can be inherited, epigenetic changes can also be inherited and linked with diseases. In MND, it is important to understand how different epigenetic changes may contribute to disease.
Dr Ekaterina Rogaeva from the University of Toronto will present her lab’s research on epigenetics in MND. The group are studying identical twins over time, where one twin has MND and the other does not, to understand why the disease develops in one but not the other when they share the same DNA. This research has identified epigenetic changes linked to the MND, although further research is needed to understand whether these epigenetic changes are a cause or consequence of neurodegeneration. Dr Rogaeva will discuss the importance of combining epigenetic studies with genetic data to help explain why some people develop MND but others do not, and how advanced technologies will allow for more robust epigenetic analyses in future.
Day 2, Session 7A: RNA Biology
Investigating RNA binding proteins in MND
In order for the DNA’s instructions to be made into proteins, genes have to be copied into RNA. RNA is like a photocopy of DNA, but it is able to move around the cell, unlike DNA, and head to the factories that make proteins. The process of copying the DNA into RNA, and converting RNA into protein, requires help from lots of other proteins. These proteins, called RNA binding proteins, can misbehave in MND. For example, TDP43 and FUS are two RNA binding proteins that are strongly linked to MND and form abnormal clumps which are toxic to neurons.
Dr Gene Yeo, from the University of California, will give an oversight of his lab’s research, which explores RNA binding proteins as a potential therapeutic target for MND. Dr Yeo will discuss the RNA binding proteins that his lab has identified to be promising therapeutic targets. Additionally, he will share his research into how RNA binding proteins are affected in ageing. He will highlight the importance of this finding in potentially explaining why ageing is a risk factor for MND. This understanding of MND could lead to more effective treatments that prevent RNA binding proteins from misbehaving in MND.
Day 1: Session 4a Cell And Organelle Analyses
Imaging clumps of protein in MND and other neurodegenerative diseases
Understanding what happens in motor neurons as MND develops is important for developing treatments, but is difficult because the changes often happen over a long period of time. One of the key disease processes in MND and other neurodegenerative diseases is proteins forming abnormal clumps. These clumps form bigger clumps inside the cells. In MND, this happens to a protein called TDP-43. It is thought that the original, very tiny clumps of protein are the ones which are toxic to cells, but these clumps are very difficult to study.
Prof Sir David Klenerman, from the University of Cambridge, will discuss how these difficulties can be overcome using newly developed methods. These new methods can measure the size, shape, and structure of the tiny clumps of protein in various samples. The clumps can also be identified in blood samples, which could have potential for diagnosing MND and other neurodegenerative diseases earlier.
Prof Klenerman and his team have also developed a tool to better understand how these clumps of protein develop and spread between cells. This tool could be used to predict the pattern of protein clumps in the brain and may also help to predict the effectiveness of different treatments. Professor Klenerman will discuss how these methods and tools can be applied to both MND and Alzheimer’s.
Day 2: Session 7b ALS-FTD Pathogenesis
The contribution of reduced C9orf72 protein to MND and FTD
Changes in the C9orf72 gene are the most common genetic cause of MND and frontotemporal dementia (FTD). The changes in the C9orf72 gene can cause damage to the cell in several different ways. One way is by reducing the amount of C9orf72 protein which is produced. The consequences of this reduction in C9orf72 protein have not been studied as extensively as other ways C9orf72 gene changes can cause damage to the cell.
Prof Janice Robertson will talk about her research into how this loss of C9orf72 protein can affect the cell. Her research has shown that reductions in the amount of C9orf72 protein affect how well cells can communicate with each other, something which happens early in MND and FTD. In particular, she will discuss how a part of the motor neuron called the AMPA receptor, which is important in how cells communicate with each other, is increased when C9orf72 protein is decreased. This means that the motor neurons are more likely to be over-active, which can lead to damage. This overactivity can be reduced by blocking the AMPA receptor from working. Prof Robertson has also found evidence that mice without the C9orf72 gene (which means they will also have no C9orf72 protein), have very overactive brain cells. When these mice are treated with a drug which causes the brain cells to go into overdrive, they develop symptoms similar to MND and FTD.
Prof Robertson’s findings suggest that reduced levels of C9orf72 protein make the motor neurons more susceptible to overactivity, due to an increase in the AMPA receptor. She will highlight how restoring the AMPA receptor to normal functioning could represent a promising strategy for new treatments for C9orf72 MND and FTD.
Stay informed
You can find out more about the International Symposium on ALS/MND on the website and view the programme for this year’s event.
