 Welcome, my name is Dr. Friedrich Stein, I'm a bimacal researcher at the University of Queensland. At UQ, I support a very talented research team and I work alongside people living with motor neuron disease as we improve our understanding of motor neuron disease. Today, I hope to share with you a little bit about what is motor neuron disease. I'll talk to you about who gets motor neuron disease. And as I do so, I'll share with you some of the things researchers are doing to help people with motor neuron disease. Now, M&D is also known as ALS and it's very possible you've already heard of ALS. In 2014, hundreds of thousands of people all around the world started pouring ice on themselves. And they did this in an effort to raise awareness but also money for the research of a disease known as amiotropic lateral sclerosis. Now, it's important to recognize that amiotropic lateral sclerosis or ALS is the most common form of motor neuron disease. This picture illustrates some of the most common forms of motor neuron disease. What is important to recognize is that there are many subtypes of motor neuron disease and that all of these subtypes exist alongside a spectrum that is defined by the impact of disease on what we call the upper motor neuron and the lower motor neuron. Now, when we talk about ALS, we talk about people who have a disease that's affecting both their upper as well as their lower motor neuron. And generally speaking, these people present or these patients present with either a spinal onset form of disease or a pulver onset form of disease. Now, this can get complicated very quickly. And so I'm going to use this very simple diagram to illustrate how upper motor neurons and lower motor neurons work together to control our muscles. And of course, how these neurons then contribute to the different types of motor neuron disease. So the first neuron to recognize is the neurons in our brain. These are known as your upper motor neurons. And these are the neurons that kind of decode your movement and tell your muscles in your limbs what to do. And what's important about these neurons is that they send long projections out of the brain down through the spinal cord where they eventually talk to a second group of neurons. Now, these are known as your lower motor neurons or your spinal motor neurons. And these neurons sit in a very particular part of the spinal cord known as the anterior horn. And so sometimes they're also referred to as those anterior horn cells. Now, what's important about these lower motor neurons is the fact that they send long projections out towards your muscle. And so they effectively attach to the muscle and they communicate information that's coming from the brain to the muscle. And so working together, the neurons from the brain talk to the spinal cord and the spinal cord can talk to the muscle and ultimately this results in movement. In motor neuron disease, very early on in the course of disease, a person might find that their balance is not very good. Or as I've illustrated in this video here, someone might find that when they walk, they have difficulty lifting their toes and clearing it off the ground. In this case, this gentleman does not have motor neuron disease, but they do present with that very classical sign of foot drop, where the nerves that engage the muscles in the leg simply don't clear the foot during normal gait. This of course is very commonly seen in people who have what we call lower limb onset disease. Sometimes a patient will present to their clinic and upon examination, it's very clear that they only have upper or lower motor neuron deficits. And over time, if there is no emergence of upper or lower motor neuron deficits, a diagnosis can be made to suggest that they have one of those less prevalent forms of motor neuron disease. For example, if a patient after four years presents with no signs of lower motor neuron deficits, they may be classed as having primary lateral sclerosis. A huge challenge in motor neuron disease research is making sense of all the different subtypes of motor neuron disease, but also the variability that is associated between these different subtypes. On top of that, it's important to recognize that even within subtypes of disease, there can be huge variation in the presentation as well as the progression of disease. And of course with this comes further challenges in making sense how to treat and help people with MND. As an example, when a person is diagnosed with ALS, they told that they might survive for two to five years. But within that two to five year survival, there's a small group of people who may pass away within months following their diagnosis, whereas some individuals may live for 10 or more years following that diagnosis. It poses massive challenges for the person providing the diagnosis, for the team supporting the individual, but more importantly for the person living with motor neuron disease as they begin to plan for their future. Research teams and clinical researchers are taking on the challenges, making sense of all the different types of motor neuron disease, and they are working really hard to improve not only the diagnosis, but also to provide people with an indication of what they might expect from their MND. So I guess the question now is, who is getting motor neuron disease? In 2015, a very comprehensive survey was made of all Australians to figure out who an Australian is living with motor neuron disease. At the time it was found that about 2,100 Australians were living with MND, and it's safe to assume that a very similar number of Australians have MND today. Now looking within this group of individuals with MND, it was found that the majority of people, about 60%, were male, and so it's thought that motor neuron disease predominantly affects men. However, it's important to recognize that as we get older, as the population gets older, the prevalence between males and females with MND becomes about the same, and so really it's only in younger age that it's considered to be a male dominant disease. The other thing to recognize is that people as young as 20 have been diagnosed with motor neuron disease, and so it isn't a disease that can affect anybody across the full spectrum of adulthood. However, as is demonstrated here, the prevalence of MND does increase with age. Now what's not illiterate on this graph is that some people in Australia are more likely to get MND. When we think about the causes of MND, people very often remind that a small portion of people, about 1 in 10, will have a family history of MND. And for those individuals or familial cases of MND, people carry a gene in their family that increased their risk of motor neuron disease. Here is a very nice schematic that was presented very recently in the journal article that summarizes the testing of most common genes that contribute to motor neuron disease across different continents. The authors have provided information on sporadic motor neuron disease. So this is the information that's contained within the outer circles and familial MND. So this is disease that is observed across families and that's summarized in those inner circles. I imagine the first thing you've noticed or may have recognized is that the genetic contribution to familial disease across the different continents are quite different. For example, if we look at Asia, you'll find that within families, the majority of patients there will have a mutation in a gene known as the soju. Whereas if we compare those individuals to Australia, a majority of people in Australia with their family history of motor neuron disease will carry mutation in a gene known as the C9ORF72 gene. Now the other thing to realize is that the C9ORF72 gene is also observed in people with sporadic motor neuron disease. And so from this information, we now know that mutations in genes like the C9ORF72 gene could contribute to sporadic onset of motor neuron disease and therefore these mutations aren't necessarily carried from parent to child. Now the other thing to recognize is that the C9ORF72 gene is not just observed in motor neuron disease. In fact, a very large proportion of people who present with a disease known as frontal temporal dementia also present with the mutation in this gene. And discoveries around the association between C9ORF72 and the prevalence of motor neuron disease and dementia has led to our improved understanding that MND itself actually also exists along a spectrum of degenerative diseases that can impact things like thinking. And we now talk about people resisting across a spectrum between MND and FTD. So the other thing to recognize on this picture are the gray circles where areas shed in gray. This represents other genes that are less prevalent and therefore may not be tested for or genes that have not yet been discovered. And if you have a look at it, these gray areas are quite prevalent in both familial cases. So these are people carrying a family gene or a family history of MND as well as sporadic cases. And so with this we have to consider one of two outcomes. The first one is that not all of the genes that are known to cause motor neuron disease have yet been identified. The second outcome is that maybe something else in our environment is causing motor neuron disease and that's not necessarily directly related to a gene. Now the most likely scenario is of course that both of these factors work together to increase risk for motor neuron disease. In fact, research suggests that there are many genes out there that may not alone increase risk but work alongside each other to increase risk for MND. And just as with any other disease, for example diabetes, our genetics has a big role to play in our likelihood of developing disease through increasing our risk for getting a disease. But it's not until we start experiencing life, not until we start getting older that we accumulate all this risk. And so with time or with age, we increase the likelihood of getting motor neuron disease and of course if we carry a gene that already increases our risk for getting motor neuron disease these effects are going to be compounded up to the point where we develop the disease. Before I go today, I'd like to add that while this recording talks about MND as a disease of the brain and muscle, it's important to recognize that MND can impact other parts of the brain. Some people can impact their thinking and their emotions and it can cause high levels of apathy as well as anxiety. Added to this, MND impacts muscles differently across people with the disease and so some people experience high levels of disability, others find their breathing deteriorates rapidly whereas many people struggle to swallow and speak. And so we put together all of the different ways in which motor neuron disease can impact the individual. We have to realize that no one experience is going to be the same. For the person living with motor neuron disease, this can pose a significant challenge. To help people with motor neuron disease, a focus of research is to improve our understanding of different ways in which MND can impact a person but also come up with new and clever strategies to try and minimize the impact of disease. And ultimately, through improving our understanding of who gets MND and what causes MND, there is hope that we will develop treatments and preventions for motor neuron disease. And so as I go, I wish to thank all of the people and all of the organizations that support us as we work towards the world free of MND.