Associate Professor Justin Rubio and his team recently published research showing that DNA from nerve cells located in multiple sclerosis (MS) brain lesions mutates at an accelerated rate compared to other nerve cells. As strong inflammation occurs in MS brain lesions, it is thought that this inflammation is somehow involved in causing mutations to nerve cell DNA, which is likely to affect the function of nerve cells and their viability.
An important unanswered question is whether inflammation is the cause of the increased mutation rate in nerve cells, or whether the nerve cells have a higher mutation rate that then triggers inflammation and the damage associated with it.
To determine whether inflammation is the cause or an effect of the accelerated mutation rate in nerve cells, this project will investigate mutation rates in DNA from cells in lesion biopsy samples from people at an early stage of their MS course. The team will then compare the mutation rate of cells from these early-stage MS lesion biopsy samples with those from post-mortem MS lesions from people who had late-stage (progressive) MS. This comparison will reveal differences in mutation patterns between early- and late-stage MS lesions, including any genes impacted more than others, and will help determine if the accelerated mutation rate is already present in cells from early-MS lesions.
Outcomes from this project will transform our understanding of the relationship between inflammation in the brain, changes in DNA that builds up in individual brain cells, and MS progression.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. It is driven by an overactive immune response, where T cells (a type of immune cell) mistakenly attack myelin, the protective covering of nerve fibres, leading to inflammation and nerve damage. While genetic factors play a role in MS, environmental influences are increasingly recognised as important contributors to MS development and progression.
The effects of diet on MS risk and progression are complex and consistent evidence is lacking. However, recent research suggests that specific dietary changes may have potential to impact MS. Dr Tan’s previous studies found a link between high meat consumption and greater pro-inflammatory T cell activity in people with MS. Since meat is rich in branched-chain amino acids (BCAAs)—including leucine, isoleucine, and valine—Dr Tan and his team studied their role in immune regulation.
In laboratory models, the team discovered that a diet high in BCAAs increased T cell activity even at resting state. This was linked to stronger responses of the T cells when they reacted to specific molecules. Further laboratory experiments found that adding BCAAs amplifies the inflammatory T cell responses against myelin.
Given the important role of T cells in MS, Dr Tan predicts that increasing BCAA in the diet may worsen disease symptoms in a laboratory model of MS. To explore this, they will study (1) how varying the level of BCAAs in diets impact disease severity and (2) the specific effects of individual BCAAs—leucine, isoleucine, and valine—on disease progression.
These findings could provide valuable insights into dietary influences in MS and may pave the way for dietary strategies to help manage the disease.
Multiple sclerosis is a long-term condition where the immune system mistakenly attacks the brain and spinal cord. While we don’t yet know exactly what causes it, both genetics and environmental factors, including gut health, are thought to play a role.
Recent research has found that people with MS often have an imbalance in their gut bacteria. This imbalance may lower the levels of short-chain fatty acids (SCFAs), which are helpful molecules produced when gut bacteria digest dietary fibre. SCFAs like acetate, propionate, and butyrate are known to help calm the immune system and reduce inflammation.
This project will explore how SCFAs affect immune cells in people with MS. Dr Parkin and her team will collect blood samples from people with and without MS. Immune cells from these blood samples will be exposed to SCFAs to see how they respond. This will help to understand whether SCFAs can shift immune cells toward a more balanced, less inflammatory state.
By studying how SCFAs influence immune cells, this research could point to new supportive strategies, such as safe, fibre-based dietary supplements, to help manage immune activity and improve outcomes for people living with MS.
Upper limb weakness and fatigue are among the most common and disabling symptoms of multiple sclerosis (MS) affecting around 75% of people living with the disease. Weakness and fatigue of the arm and hand significantly impacts independence, the ability to complete daily tasks, and overall quality of life. While current treatments aim to slow disease progression, they offer little help in restoring lost strength or movement.
Dr Thorstensen’s project will test a new, non-invasive technique called paired corticospinal-motoneuronal stimulation (PCMS), designed to strengthen the communication between the brain and spinal cord. PCMS uses carefully timed electrical signals and magnetic brain stimulation to increase the responsiveness of the nerve cells in the spinal cord that control muscles (motoneurons). In previous research on spinal cord injury, PCMS has been shown to boost muscle strength by up to 50%. This study is the first to apply PCMS to people with MS.
Dr Thorstensen’s team will study this technique in individuals with mild-to-moderate MS to see whether it will increase the responsiveness of motoneurons and whether changes correlate with improved symptoms in regard to weakness and fatigue. By comparing real and mock stimulation, the team will generate early evidence that will lead to new rehabilitation tools for MS.
Ultimately, the goal is to develop PCMS into a low-cost, widely available therapy that improves motor function, reduces disability, and enhances quality of life for people living with MS.
People living with multiple sclerosis (MS) often experience worsening symptoms and reduced treatment effectiveness when also living with overweight or obesity. Healthy lifestyle changes, including exercising more or healthy eating, can improve MS outcomes, but not everyone responds the same way. One possible reason for this difference is the microbiome, which is the community of bacteria that live in and on our bodies. While gut bacteria have received a lot of attention, the mouth also hosts a large and important microbiome that could impact health, especially in people living with MS.
Recent research shows that the oral (mouth) microbiome may play a role in inflammation and neurological diseases, but very little is known about how it behaves in people living with MS or how it changes with lifestyle improvements. Dr Olivia Wills and her team will investigate how a weight loss program focused on diet, exercise, and behaviour change therapy, affects the oral microbiome in people living with relapsing remitting MS over a 6-month period.
By analysing saliva samples collected from the mouth at the start of the weight loss program and six months later, Dr Wills aims to understand whether helpful bacteria increase and harmful bacteria decrease. She and her team will also investigate whether fatigue and mood improve. This study builds on an existing clinical trial and will help Dr Wills and her team learn if improving the oral microbiome is part of the benefit of lifestyle changes for people living with MS. This could contribute to more personalised, microbiome-targeted care in the future.
Multiple sclerosis (MS) is a disease that damages myelin, the protective layer around nerves in the brain and spinal cord. When myelin is damaged, nerve signals don’t work properly, leading to various symptoms.
Unfortunately, there are no treatments that can fully protect or repair myelin. Certain immune cells in the body, like microglia and macrophages, help support myelin-producing cells (oligodendrocytes), but we still don’t fully understand how.
Dr Monokesh Sen and his team believe that tiny particles released by these immune cells, called extracellular vesicles, play an important role in cell communication and may help with myelin repair.
To investigate this, they will collect blood samples from both people with progressive MS (a form of MS with ongoing inflammation, nerve damage and impaired myelin repair) and individuals without MS. From these samples, they will extract immune cells called peripheral blood mononuclear cells, grow them in the lab, and turn them into macrophages. These macrophages naturally release extracellular vesicles (MEVs), which we will collect using a specialised process called ultracentrifugation.
Next, the team will administer MEVs into a laboratory model and track where they go in the body and at the cellular level. They will then test their effects in another MS laboratory model to see how they influence oligodendrocytes and myelin repair.
By understanding how these MEVs affect myelin regeneration, Dr Sen and his team hope to find new ways to repair myelin and develop future treatments that could improve the lives of people with MS.
A person’s risk of developing multiple sclerosis (MS) is influenced by both their genes and environmental factors. Infection with the Epstein-Barr virus (EBV), which causes glandular fever, has been shown to be a necessary step in the development of MS, although most people who contract EBV never go on to develop the disease.
This suggests that differences in how people’s immune systems respond to EBV, which are strongly influenced by genetics, may play an important role in MS risk.
This project will compare EBV, MS, and immune-related measures in people with either a ‘high’ or ‘low’ genetic risk of developing MS. To achieve this, Dr Stacey and the research team will employ an innovative study design called recall by genotype, a method that selects participants based on their genetic risk.
This approach has not yet been used in MS research, either in Australia or internationally. Unlike most studies that compare people with and without MS, none of the participants in this study will have the disease. This means any differences observed are more likely to reflect early biological processes that contribute to MS, rather than changes caused by the disease itself.
The aim of the project is to test how feasible it is to use this approach in MS research and to prepare for a larger study in future. The team will: (i) refine methods for selecting and inviting participants based on genetic risk; (ii) explore the ethical, legal and social implications of using genetic information for research recruitment; and (iii) fine-tune laboratory methods to measure key immune and viral markers.
This work may improve our understanding of how MS develops and could help identify new ways to predict, prevent or treat the disease.
The exact cause and mechanisms underlying the development of multiple sclerosis (MS) are poorly understood, but we know it is driven by a complex interplay between genes and environmental factors.
The genetic risk factors of MS strongly implicate immune cells and vascular cells (cells of the heart and blood vessels) in driving MS initiation. Despite this, few studies have explored the role that vascular cells play in disease development.
Dr Alastair Fortune and his team aim to determine how MS genes can alter pericytes (brain vascular cells) even before immune cell activation can damage them. They will generate pericytes from induced pluripotent stem cells (iPSCs) – immature cells that can produce any cell type in the body – from people with and without MS, and compare their function.
Blood flow is altered in people with MS, and the team will determine whether this is due to DNA-programmed differences in MS pericytes. They will also investigate how pericytes respond to an MS lesion-like environment.
This project aims to determine whether and how pericytes contribute to blood vessel abnormalities in people with MS.
Poor sleep is common in the general population, but it’s even more common among people living with multiple sclerosis (MS). Sleep problems can have a serious impact on health and quality of life, and there is an urgent need for better treatments that improve both sleep and MS symptoms.
Researchers often assess sleep using survey questions, but these can miss important details. Sometimes activity monitors (similar to research-grade Fitbits) are used, but typically only for a week; this might not be long enough for people with MS, whose symptoms can change from day to day. Despite this variability, researchers don’t usually collect symptom information frequently enough to detect these changes.
This project will focus on getting the basics right by collecting high-quality, meaningful data on sleep in people with MS. Dr Laura Laslett’s research will test whether using activity monitors to track sleep and a symptom-tracking app (MySymptoMS) is practical and acceptable for people living with MS. She aims to find out whether these tools need to be used for longer than a week, whether some people are more likely than others to use them, and whether they provide different or better information than traditional surveys.
These insights will help determine whether these tools should be included in future clinical trials aimed at treating poor sleep in MS.
Multiple sclerosis (MS) is characterised by inflammation, loss of nerve protection (demyelination), and nerve cell damage (neurodegeneration). Currently, no treatment specifically reduces or reverses nerve-related disability in MS, representing a significant unmet need.
This project explores a potential new therapy using T-regulatory cells (Tregs), a type of immune cell. The research builds on previous findings showing that Tregs are replenished after autologous haematopoietic stem cell transplantation (AHSCT) in people with MS, a process believed to support long-term remission. Preliminary studies in laboratory models suggest Tregs may promote nerve repair, which this project aims to explore further.
Dr Malini Visweswaran and the team will examine whether Tregs from a person’s own cell transplant retain the ability to promote nerve repair, or if Tregs from people without MS might be more effective.
This research could pave the way for novel treatments targeting nerve repair to reduce disability in people with MS.
