MND Australia grants commencing 2025

Bill Gole MND Research Fellowship

In MND, one key reason motor neurons die is the accumulation of toxic protein clumps inside them. Normally, the body clears away this harmful “trash” through a natural process called autophagy, but in MND, this process becomes impaired. My project focuses on developing an innovative therapy using tiny proteins called peptides, designed to enter the brain, target motor neurons, and restore autophagy. These peptides have already shown promise in MND mouse models by enhancing autophagy and extending survival. By refining these peptides and testing them in various MND models, we aim to protect motor neurons and slow or even halt disease progression. This research could lead to new treatments that improve the quality of life for people living with MND.

MND Australia Postdoctoral Fellowship

Recent advances in transcranial magnetic stimulation (TMS) technology, a non-invasive method of assessing brain function, have enabled the assessment of new excitability properties in motor neuron disease (MND). Cortical dysfunction occurs early in the development of MND and heralds a faster rate of disease progression, greater functional disability and more prominent weakness. The research encompassed by this MND Australia Postdoctoral Fellowship will assess new measures of cortical excitability dysfunction in MND patients to further our understanding cause of the disease.

Scott Sullivan MND Research Fellowship

People living with motor neurone disease (plwMND) are known to have alterations in their body fat composition and metabolism. Fat molecules (also called lipids) are essential for the maintenance of motor neurons and muscles. Recently, I discovered that a subset of these lipids is unique to MND. However, this data is preliminary, and further tests will be necessary to assess if this is the case in a greater cohort of plwMND. We will assess the normal and abnormal ranges of the lipids that can then be communicated with specialists to be a biomarker for disease. Furthermore, we will assess the lipid biomarkers in a population of asymptomatic gene carriers to assess if these lipids are abnormal before symptom onset. Once this research is complete, I hope that this can help clinicians assess if drugs have a desired effect and how disease is progressing. This will in turn help with drug development and treatment strategies in the future.

Charcot, supported by Fat Rabbit

The numerous proteins linked to ALS share the interesting ability to behave like a liquid inside cells. When proteins behave like this, we call them protein condensates. Imagine these protein condensates as very much like the blobs in a lava-lamp. The blobs move around, break apart and can join up with other blobs seemingly at random and this behaviour is required to keep motor neurons healthy. Recently, we discovered that a subtle drop in pH, a measure of acidity or alkalinity, inside cells prevents the formation of protein condensates. This is significant as there is a gradual decrease in pH (acidosis) in our brains and spinal cords as we age and this coincides with the emergence of disease. Our study aims to determine whether this decreased pH changes the normal liquid behaviour of ALS proteins to trigger abnormal protein behaviour that can cause the loss of motor neurons. Our findings will help us better understand the early molecular triggers of disease and spur research in pH modulation as new treatments.

Dr Paul Brock MND Research Grant

Mobile DNA or ‘jumping genes’ make up nearly half of a person’s DNA and can affect how cells function. Some of these pieces of mobile DNA are more active than others and their increased activity has been identified in people with motor neuron disease (MND). Pieces of mobile DNA are large and repeat themselves throughout a person’s DNA which make them difficult to study with current techniques. However, a new type of technology will allow us to analyse these pieces of mobile DNA in more detail and with greater accuracy. We will use this data to identity the specific pieces of mobile DNA that are the most active in people with MND. We hope to generate a mobile DNA signature to identify those people who have the most active mobile DNA and could potentially benefit from treatments available to reduce this activity.

Linda Elphick MND Research Grant 

In MND, motor nerve cells become hyperactive, which causes the release of molecules that become toxic to the nervous system. Some nerve cells are particularly sensitive to breaking down as a result of this toxic environment. The long nerve fibres that connect nerve cells and our muscles are also targets for this breakdown, which may trigger independently from the rest of the motor nerve cells. Protecting nerve cells from breaking down is dependent on protecting both the cell body itself, as well as their long fibres. We have identified a range of changes that occur to the nerve cell fibres that contribute to their breakdown after nerve cells become hyperactive. We seek to understand these changes further, and aim to counteract the changes to prevent the fibres from degeneration in MND. This project will test molecules to prevent nerve fibre break down in MND and provide a pathway to preclinical drug development for MND.

Murray Geale MND Research Grant

Our project aims to develop a new "brain in a dish model" for studying MND. Using blood cells from people living with MND, we generate microglial cells—the brain’s immune cells—and combine them with lab-grown brain-like structures (organoids) derived from stem cells. This advanced “mini-brain” system will allow us to test potential treatments in a way that closely mimics the conditions of the human brain. By focusing on immune pathways involved in inflammation and nerve damage, we aim to identify more effective and precise therapies for MND. Ultimately, this research could lead to a more personalised treatment approaches.

Ian Sneddon Two Rivers Run MND Research Grant

In almost all MND patients, a protein called TDP-43 becomes dysfunctional, failing to process RNA properly as it does in healthy individuals. This dysfunction disrupts critical cellular processes eventually leading to the formation of toxic protein aggregates. This project will investigate how a specific protein modification, called phosphorylation, may drive early changes to TDP-43’s ability to bind RNA and contributes to disease progression. To achieve this, we will first use neurons grown in the lab to examine how phosphorylated versions of TDP-43 interact with RNA. Next, we will use our unique transparent zebrafish model to see phosphorylated TDP-43’s effect in living motor neurons. By uncovering how these early changes lead to disease, we will identify new targets for delaying or altering the course of MND, providing hope for better treatments.

NTI MND Research Grant

People with ALS have abnormal aggregation of a protein called TDP-43 in brain cells, contributing to disease progression. Recent research suggests that TDP-43 may also affect the function of the blood-brain barrier (BBB), which is a crucial defence system located in the blood vessels of the brain. How TDP-43 affects the BBB in ALS is not well understood. Here, we will use human stem cells, obtained from people with ALS to generate laboratory models of the BBB to investigate the role of TDP-43. We will investigate if abnormal TDP-43 in ALS leads to breakage of the BBB, leading to increased leakage of substances into the brain and whether this leads to increased inflammation in the brain. Understanding this relationship could help better understand ALS progression and develop new treatments for ALS.

MonSTaR MND Research Grant

There is no cure and few effective treatments for Amyotrophic Lateral Sclerosis (ALS). ALS is caused by degeneration of motor neuron terminals from skeletal muscle and motor neuron death. Use of stem cells converted from patient skin or blood can replace obtaining human motor neuron terminals directly from patients. This project aims to find drugs that can reduce denervation and prolong motor neuron survival with a robot-assisted stem cell neuro-muscular junction screen, and potentially slow the progression of ALS. 

The Elizabeth and Peter John Cahill MND Research Grant

Traditionally, the focus in MND has been on dying nerve cells. However, the unsung heroes of the nervous system are called “glial cells”, which provide nerve cells essential functional support. We will examine how a type of glial cells called “astrocytes” handle waste through a process named autophagy. Our preliminary findings indicate that astrocyte autophagy waste clearance is overactive in MND. Using transgenic mouse models, we will normalize this process, thereby making astrocytes provide better support to nerve cells, helping them live healthier and thereby longer. Outcomes will help us better understand causes and guide new treatments for MND.

Peter Stearne Familial MND Research Grant

Everyone has two FUS gene copies, if one copy carries a mutation, patients are affected by MND. An existing therapeutic reduces all copies of the FUS gene. We have developed therapeutics that target only the mutant copy, stopping the production of toxic protein and allowing normal FUS protein to be produced to fulfil its functions. We have also developed a therapeutic that reduces all FUS but has a different mechanism of action and chemical properties that improve safety. This project will examine the effects of our therapeutics on neuronal health and function in motor neurons grown from FUS-ALS patient cells.

Daniel Veysey MND Research Grant

While ALS can be inherited, environmental factors are believed to play a key role in determining who develops the disease and how it progresses, especially in sporadic cases. This is evident in identical twins: despite sharing the same genes, only one may develop ALS. Identifying these environmental triggers has been challenging because traditional studies often rely on questionnaires and patient records, which have significant limitations. This project takes a fresh and innovative approach. By employing a novel assay in an innovative way, it will begin systematically investigating how environmental and workplace factors contribute to both sporadic and familial ALS. At the same time, it aims to lay the groundwork for exploring how genes and the environment interact, setting the stage for uncovering the mechanisms behind these processes. This work could provide valuable new insights and accelerate progress in understanding and reducing the risk of ALS.

Col Bambrick MND Research Grant

There is an urgent need for new MND treatments. This proposal explores a novel strategy using drugs that target the electrical properties of motor neurons, the cells affected in MND. These properties are critical component of the brain's communication system because they regulate nerve activity. We will examine whether these drugs are protective in human cells and mice that develop MND: the first step in their development for MND patients. Our approach is exciting because these drugs are ‘repurposed’, meaning they are already on the market for other conditions. This will expedite their development as a new treatment for MND.

Superball XVII MND Research Grant

We have identified a subgroup of sporadic MND patients with a unique molecular signature in the cerebellum, a brain region with a lesser-known role in MND. Interestingly, this subgroup demonstrates the same pattern of hallmark TDP-43 pathology as MND patients who carry a mutation in the C9orf72 gene. We aim to uncover whether this sporadic MND subgroup, encompassing around one-third of all MND cases, shares other similarities with C9orf72-linked MND. Identification of similar genomic (DNA) or transcriptomic (RNA) signatures means that individuals belonging to this sporadic MND subgroup may have common therapeutic targets to the major genetic cause of MND

Eileen Grace Bignall MND Research Grant

This project will bring together people living with MND, their carers, clinical care teams, sleep scientists and engineers to refine and test a new mattress sensor device that will measure breathing in more detail that has previously been possible. This will allow breathing problems and sleep to be routinely assessed in the home without any intrusive worn sensors. Co-design and pilot tests through this 1-year project will accelerate translation into more comprehensive and streamlined respiratory-sleep medical care for people with MND.

MND South Australia MND Care Research Grant

Research has found that up to 50% of people living with MND may experience cognitive and behavioural changes as part of the disease. Currently, we don’t know how families, who are experiencing MND, would prefer to learn about and manage cognitive and behavioural changes. This means that the ways we currently assess for and manage cognitive and behavioural changes are inconsistent, or it may even mean that these changes are not detected or discussed at all. The Flinders University team of researchers, who work in the MND space, will partner with people with MND and their families, to determine ways that they would prefer to learn about and manage cognitive and behavioural changes. The research team aim to understand what suits everyone in the family and how care can be optimised to meet their needs. The outcomes of this research project will help to develop clinical frameworks and educational resources for people with MND, their families and MND clinicians. These resources will support families to work together with their health care team to navigate cognitive and behavioural changes, in ways that best suit their individual needs and preferences.
 

Jenny Simko MND Research Grant

In SOD1-linked MND patients, as well as many sporadic MND cases, the SOD1 protein folds incorrectly, forming toxic aggregates that interfere with normal neuronal functioning. In this project, we will compare the genetic profiles of people with MND and healthy individuals in cells taken from a skin biopsy and use these cells to test the effect of our SOD1 suppression therapy. The findings will allow us to rapidly identify sporadic patients with genetic profiles that resemble SOD1-linked cases who may benefit from SOD1 suppression in future clinical trials, making our anti-SOD1 drug widely accessible to MND patients.

In almost all people living with MND, a protein called TDP-43 malfunctions, forming toxic clumps and losing its ability to perform critical functions in cells. There is currently no way to stop or treat this, however, emerging evidence suggests that another protein called ataxin-3 may be able to help. This project will be the first to establish how the ataxin-3 protein may have beneficial effects against toxic, malfunctioning TDP-43 protein in both human cell and zebrafish models of MND. This knowledge could guide future research on a treatment for malfunctioning TDP-43, which would likely benefit most people living with MND.

Emerging evidence suggests that small fat-storing structures in cells, called lipid droplets, may play a role in MND. This project aims to explore how changes in fat metabolism are connected to neurodegeneration and inflammation in MND using models and advanced techniques in neuroimmunology, fat metabolism, and computational biology. By mapping these changes in unprecedented detail, the project hopes to uncover new clues about the causes of MND and identify potential targets for future treatments. This research will not only improve our understanding of MND, but also help in developing better therapies for those affected by the disease.