It’s that time of year again when we’re counting down to the annual International Symposium on ALS/MND! This year marks the 35th Symposium, the largest scientific and medical conference specific to ALS/MND, and throughout November we will be posting blogs to give you a preview of some of the research being presented at this year’s event. This global event gives the MND research community the chance to share their work, exchange knowledge and foster new collaborations.
This year, the Symposium is being held in Montreal, Canada from the 6th– 8th December and there is also a virtual option for attendance. The virtual attendance will allow delegates to watch select sessions live, with on demand access for all sessions available after the event (on demand access will also be available to those who attend in-person).
Last year the symposium was attended by over 1300 delegates from 44 different countries, including researchers, healthcare professionals and people from the wider MND community. We look forwarding to hosting this hugely important event and hope to see lots of you there! There’s still time to register if you haven’t already!
Each year we invite plenary speakers who are experts in their fields to provide an overview on topics across MND research and clinical practice. This year we have 20 plenary speakers talking about ALS/MND who will cover a wide range of topics from understanding more about the biology of MND to improving care and support for people with and affected by the disease. Over the next month, we will be taking a closer look at each of our ALS/MND plenary speakers this year and giving you a snapshot of the topics they will be discussing.
Day 1, Session 4A: In vitro models
New treatments for people living with ALS are urgently needed, but first we need to better understand the biological mechanisms that cause some people to get the disease so that we can develop new therapies that target these mechanisms.
Professor Jeroen Pasterkamp, from UMC Utrecht in the Netherlands, uses different types of research to explore how motor neurons grow and what goes wrong in ALS. He uses advanced lab techniques and disease models ‘in a dish’ that mimic different cell functions.
In his talk ‘ALS-in-a-dish: modelling motor neuron disease using advanced human in vitro models’, Professor Pasterkamp discusses his work on developing a range of lab-grown human cell models using advanced techniques. These models are created from stem cells (called induced pluripotent stem cells or IPSCs) and can provide detailed information about how cells behave. The models include specific cell types, like motor neurons and muscle cells, as well as more complex systems where different cells interact, either in small devices or in 3D structures that mimic real tissues, known as organoids. Using organoids, several 3D models of the brain and nervous system have been developed allowing Prof Pasterkamp and his team to study how cells communicate with each other. These models show key signs of ALS, making them useful for understanding the disease better and finding new treatments.
Day 2, Session 5A: Cell biology and pathology
Neurons need a constant supply of energy, which is delivered through the blood vessels in the brain. They rely on oxygen and glucose to send signals properly. When the blood vessels don’t work as they should, it can lead to neuron damage, and this often happens before the neurons are impaired. However, we still don’t fully understand how this process works in ALS. Previous research has shown early signs of problems with the blood-brain barrier, reduced blood flow, and changes in blood vessels in both people with ALS and animal models.
In his presentation ‘On brains and vessels. How vascular mechanisms contribute to ALS neurodegeneration’, Dr Sebastian Lewandowski from the Karolinska Institute in Sweden, will talk about how it has been shown in animal models that these issues with the blood-brain barrier happen before symptoms appear and can speed up the onset of disease. Lower blood flow and less glucose reaching the brain are linked to faster disease progression. Changes in the blood vessel network can also affect how long someone survives, and this is the target of ongoing preclinical trials. He will discuss how understanding these vascular problems helps us to understand ALS, identify early warning signs and develop new treatments for both inherited and non-inherited forms of the disease.
Day 2, Session 6A: Proteostasis and proteotoxicity
The build-up of abnormal, misfolded proteins is a common feature in many neurodegenerative diseases. These misfolded proteins are thought to cause damage to neurons, with directly or indirectly. Recent research suggests that these proteins can spread from one cell to another, worsening the disease. There is also growing evidence that these proteins can have different shapes or ‘strains’, which could explain why these diseases vary so much from person to person.
Professor Virginia Lee, from the Center for Neurodegenerative Disease Research in the United States, will talk about how in Alzheimer’s and similar diseases linked to ageing, the tau protein, which is usually soluble (meaning it normally dissolves in the liquid inside cells allowing it to move around and perform its functions properly) forms clumps called neurofibrillary tangles. In Parkinson’s and related conditions, the α-synuclein protein, which is also normally soluble, forms clumps called Lewy bodies inside nerve and glial cells (glial cells help to support and protect neurons). This harmful clumping of protein cells is also seen in frontotemporal dementia, when TDP-43 clumps in the cytoplasm of cells. In her presentation ‘Transmission of misfolded proteins in neurodegenerative disorders: A common mechanism of disease progression’, Professor Lee will also discuss how she has developed models to study how tau, α-synuclein, and TDP-43 proteins spread between cells and change shape (‘strain’ hypothesis) as they do. These models may help us to understand how these protein clumps worsen and spread over time and will support the development of new therapies for these are-related brain diseases.
Day 2, Session 7C: Antisense and siRNA-based therapeutic strategies
There are several genetic-based treatments being developed for rare neurological diseases, including antisense technology, gene therapy and gene editing. One of the more advanced approaches is using antisense oligonucleotides (ASOs) which are synthetic molecules designed to bind to RNA and change how it functions. They can target both protein-coding RNA (RNA that contains the instructions to make proteins) and non-coding RNAs, which make them more flexible for drug development compared to traditional drugs.
In his talk, ‘Antisense based therapy for rare neurological diseases’, Dr Frank Bennett from Ionis Pharmaceuticals Inc in the United States, will discuss how the approval of the drugs nusinersen (marketed as Spinraza) for spinal muscular atrophy and tofersen (marketed as Qalsody) for the SOD1 inherited form of ALS has shown that antisense drugs can be effective for treating motor neuron diseases. The potential use of antisense technology for other rare brain diseases and developmental disorders is also being explored.
Day 2, Session 8A: RNA biology
Understanding the causes of neurodegenerative diseases, particularly the genetic mutations that lead to these, and how the molecular signatures of these conditions change over the course of ageing and disease, is vital in helping to uncover specific markers of disorders being studied.
Professor Hemali Phatani from the New York Genome Center in the United States talks about how her team have used a multidisciplinary approach to study this question by combining data from both living and deceased individuals in her talk ‘Using spatial genomics to study the central nervous system in health and disease’. She will discuss how they have analysed genetic information at different levels, from single cells to whole tissues, with the goal of understanding the molecular changes that happen in various types of cells during ageing and disease. Prof Phatani has already applied these methods to several diseases, including ALS-FTD. The large datasets that this work will create will help to find specific molecular changes linked to cell and tissue damage in ALS-FTD. The aim is to share the data with other researchers so they can use it to discover makers for their own diseases.
Stay informed
You can find out more about the International Symposium on ALS/MND on the website and view the full programme for this year’s event.
You can follow our research account on X where we post about research updates and will be posting throughout the Symposium using the hashtag #alsmndsymp.
