Multiple sclerosis (MS) is a disease that affects the myelin in the brain. Myelin is the fatty layer around neurons (nerve cells) that act like insulation on electrical wire and helps neurons send messages through the brain effectively.
Building and maintaining myelin requires lots of energy, and that makes it vulnerable to damage from inflammation and free radicals (unstable molecules that can affect healthy cells).
Copper is an essential metal that helps cells produce energy and antioxidants, which helps to maintain myelin health and protect cells from damage. When copper cannot properly enter the brain, myelin becomes damaged, suggesting it may play an important role in MS.
While the cause of MS isn’t known just yet, it is believed to involve both genetic and environmental risk factors. Among the greatest risk factors for MS is prior infection with Epstein-Barr virus (EBV). Another risk factor is vitamin D deficiency. Additionally, patients with MS are likely to have fewer ‘good bacteria’ in their gut, and more ‘bad bacteria’. This research project will test the hypothesis that these three environmental factors have something in common – they interact with copper.
There is new evidence that copper absorption depends on a healthy assortment of gut bacteria, and vitamin D helps incorporate copper into cellular antioxidants. Additionally, new evidence suggests that if copper is disrupted, myelin may ‘look like’ Epstein-Barr virus to the immune system resulting in the immune system attacking the myelin. Historically, this has been difficult to study, but due to new technical advances it is now possible to take images of copper in the brain.
Dr Lins and her team aim to determine if copper is at the core of MS environmental risk factors, with hopes this will lead to new treatment and prevention strategies.
A key driver of progression is neurodegeneration, the damage and loss of nerve cells. This close link between neurodegeneration and disease progression underscores its importance as a treatment target. Despite available treatments for multiple sclerosis (MS), protecting the nerves, or “neuroprotection”, remains a significant unmet need, particularly for those living with progressive MS.
In this project, Dr James Hilton and his team are studying a group of compounds called bis-thiosemicarbazones (BTSCs) for their ability to protect the nerves. These compounds have already shown promise in several neurological diseases, including motor neurone disease and Parkinson’s disease, especially through a compound called copper-atsm, or Cu(atsm). They have also shown that Cu(atsm) improves outcomes in models of MS by boosting growth of the protective myelin coating around nerves, reducing lesion size, and supporting nerve repair. It also corrected several copper‑related problems seen in progressive MS.
There is additional evidence that Cu(atsm) may protect nerves by stopping a type of cell death called ferroptosis, driven by iron. Since ferroptosis may play a role in MS, this could be another useful pathway for treatment. Although Cu(atsm) seems to act on both copper imbalance and ferroptosis, it is still unknown how much each of these actions contributes to neuroprotection.
To explore this, Dr Hilton will develop and test new BTSC compounds in cell culture. These compounds will be selected based on their ability to target copper imbalance, ferroptosis, or both. The most promising compounds from each group will then be tested in a model of MS to assess their therapeutic benefit and confirm they act on the intended biological pathways while providing neuroprotection. By understanding how these mechanisms contribute to MS, Dr Hilton and his team aim to discover new and more effective BTSC compounds that could eventually move into clinical testing.
The number of people with overweight/obesity is increasing worldwide. This is accompanied by an increasing number of people with obesity-related chronic disease, including multiple sclerosis (MS). Overweight/obesity is associated with increased MS risk, disease activity, progression, and associated symptoms, and poorer treatment response to disease modifying therapies.
Diet is a risk factor for obesity, and potentially for MS, that people are empowered to change. Macronutrients are the carbohydrates, fats and proteins in food. Changing the macronutrient composition of a diet, particularly carbohydrate and fat, is at the core of the diets promoted for weight loss/management and for people with MS. Previous studies have investigated links between dietary macronutrient composition and MS risk and progression, with varied methods and findings. Most studies have focused on single macronutrients or a handful of dietary patterns where macronutrient composition is manipulated. But they have not considered the effects of all macronutrients together, which is a possible reason for the inconsistent conclusions of those studies.
The Geometric Framework for Nutrition (GFN) is a way of analysing diet that considers the effect of all the macronutrients together, including how they affect each other.
For example, it has shown that weight loss with low carbohydrate diets is partly due to reduced overall energy intake - not because of the reduced amount of carbohydrate per se, but because of increased protein proportion in the diet.
In this project, Dr Hajar Mazahery will apply the GFN to investigate the relationships between macronutrient intake, quality of macronutrients, total energy intake, overweight/obesity, and MS risk and progression. She and her team will use studies from four countries (Australia, United Kingdom, Brazil and Japan), representing individuals with various ethnic backgrounds. The project will produce high quality evidence to support the development of guidance on macronutrients for people with MS. The impact will be substantial, empowering people to make positive changes to their diet.
Inflammation in the brain known as "smouldering inflammation” plays a crucial role in the progression of MS. Unlike the more visible acute inflammation, smouldering inflammation is a slow and persistent process that contributes significantly to nerve damage and disability in people with MS. Current treatments mainly target the acute episodes but do not effectively address this chronic, underlying inflammation.
Mr Samuel Klistorner and his team will develop and refine advanced imaging techniques to detect and monitor smouldering inflammation. By using advanced MRI methods, the team plans to track the subtle changes in brain lesions over time. This will help with understanding how these lesions expand and contribute to the overall progression of MS.
Additionally, the research will explore the potential of combining various diagnostic tools, such as Visual Evoked Potentials (VEP) and Optical Coherence Tomography (OCT), to create a comprehensive biomarker for smouldering inflammation. This biomarker would allow for more precise and early detection of disease progression, ultimately leading to more personalised and effective treatment plans for MS patients.
The ultimate goal is to improve the quality of life for individuals living with MS by providing better tools for diagnosis and monitoring, which can lead to more targeted and effective treatments. By advancing our understanding of smouldering inflammation and developing these innovative techniques, Mr Klistorner and his team hope to significantly impact patient care and outcomes in the fight against multiple sclerosis.
MS is a disease that damages myelin, the protective coating around nerves in the brain and spinal cord. This damage disrupts nerve signals and causes various neurological symptoms. Currently, no treatment can fully protect or repair myelin effectively. Dr Monokesh Sen and his team are researching how certain immune cells, specifically microglia and macrophages, support myelin-producing cells, known as oligodendrocytes, which are essential for myelin repair. The team believes that small particles released by these immune cells, called extracellular vesicles (EVs), play a critical role in this process.
Dr. Sen’s project will investigate how these microglia/macrophage-derived EVs (MEVs) might help communicate with and support oligodendrocytes. The team will first collect blood samples from both people with MS and healthy individuals, isolating specific immune cells to generate macrophages in the lab. The MEVs released from these lab-grown macrophages will be collected and analysed for their protein and lipid content, using a special process to separate cells, called ultracentrifugation. By comparing MEVs from people with MS and healthy controls, Dr. Sen’s team hopes to identify potential biological markers, or biomarkers, related to MS severity.
Additionally, the team will study how MEVs influence the growth and maturation of oligodendrocytes in lab settings and laboratory models of MS. This research aims to provide new insights into the underlying processes that promote myelin repair. This could lead to future treatments that help people with MS rebuild damaged myelin and improve their symptoms.
Multiple Sclerosis (MS) is a disease that can cause nerve damage even before noticeable symptoms appear. For doctors, this early phase is like solving a puzzle with missing pieces—they see unexplained brain abnormalities but lack a full picture. This project aims to fill in these gaps using advanced blood tests, patient information, electronic health records and cutting-edge technologies such as artificial intelligence (AI).
Dr Seyhan Yazar and her team are focusing on the ‘prodromal phase’ of MS. This is the stage where vague symptoms may occur but don’t yet meet the criteria for a diagnosis of MS. These symptoms, such as mild neurological or cognitive issues such as migraines or confusion, occur within the general population as well, which can make it difficult to identify as a symptom of MS.
By analysing large datasets and identifying specific patterns, Dr Yazar and her research team hope to help doctors identify MS more accurately in its early stages.
One major goal of the project is to find signs in the blood, called biomarkers, that could reveal MS before typical symptoms appear. When combined with brain scans, these biomarkers could help doctors diagnose MS earlier, especially in people who are at higher risk, such as those with unusual findings on their brain scans.
By gaining a clearer understanding of MS during its early stages, doctors may be able to diagnose and treat patients sooner, potentially preventing long-term damage and improving their quality of life. This research may also open the door to new preventative measures for MS in the future.
Over half of people with multiple sclerosis (pwMS) are aged over 50. There is an urgent need for evidence-based treatment and earlier detection of disability progression in older pwMS. Whilst existing disease modifying therapies (DMTs) have demonstrated efficacy for inflammatory aspects of MS at early disease stages, their effectiveness in neurodegeneration at later stages of MS is limited. Combined with the greater risk of events such as infections and malignancy with age, there are concerns about using DMTs to treat older pwMS. Current clinical decision-making can be inconsistent, opinion-based and may expose older pwMS to unnecessary treatment.
Dr Yi Chao Foong and his team aim to establish the effectiveness of DMTs in older pwMS. They will also investigate the risk of side effects related to DMTs in older pwMS, and subsequent risk of disability progression. Understanding the balance between therapeutic benefits and risks is crucial for the use of DMTs in this population. The team also aims to identify digital monitoring tools that may predict early identification of progression or treatment failure, ultimately improving patient outcomes.
Dietary fat is one of the most controversial topics in diet and MS. Three of the most common diets marketed to people with MS have dietary fat at the core of their recommendations: Overcoming MS, Swank, and Wahls Paleodiets. However, those diets have conflicting views on dietary fat, with the Overcoming MS and Swank diets promoting a low-fat approach, and the Wahls Paleo diet promoting high-fat intakes.
Dr Barbara Brayner and her team will investigate the associations between dietary fat and the risk of MS and MS progression. They will use data from four countries (Australia, UK, Brazil and Japan) representing individuals with various ethnic backgrounds. Dr Brayner’s project will include data from Australia’s AusImmune and AusLong studies.
This project aims to produce high-quality evidence to support the development of guidance regarding dietary fat for people with MS. The impact could be substantial since making dietary changes is something people can implement in their daily lives.
Health economics is concerned with maximising quality of life through the effective use of healthcare resources. Health economists provide evidence that contributes greatly to MS advocacy and government funding decisions. Therefore, health economics is an essential component of MS research.
Mr Glen Henson and his team aim to use health economics to enhance our understanding of the quality-of-life impacts of MS. They will use existing world-class MS databases to:
The team will also work on improving current health economics methods, by encouraging a more patient-centred approach to MS health economics, examining new tools for measuring quality of life, and developing benchmarks to assist MS researchers in interpreting health economics data.
MS is a devastating neurological disease that causes the body's immune system to attack the protective coating around nerve fibres (myelin) in the brain and spinal cord. This leads to communication problems between the brain and the rest of the body, resulting in a range of disabling symptoms.
As MS progresses from the initial relapsing remitting phase to the secondary progressive phase, the damage becomes more widespread and severe. This is characterised by increased demyelination (loss of myelin) and neurodegeneration (damage to nerve cells) in the brain and spinal cord. This progressive nerve damage causes significant cognitive impairments for people living with MS.
Interestingly, researchers have found that levels of a protein in the brain called tau are significantly elevated in people with progressive MS. Tau is also implicated in other neurodegenerative diseases like Alzheimer's disease. This suggests there may be a link between tau abnormalities and the nerve damage that occurs as MS worsens.
One potential explanation is the role of a protein called BIN1, which is selectively expressed in myelin-producing cells. Studies have shown that BIN1 may play a key part in regulating tau processing.
Dr Tse’s project will investigate the relationship between tauopathy (abnormal tau), demyelination, and neurodegeneration in progressive MS. By closely examining the patterns of tau, BIN1, and immune system activity, he and his team hope to uncover the underlying biological mechanisms driving nerve damage in later-stage MS.
These insights could pave the way for therapies that target tau or BIN1. Such therapies could potentially slow down or even halt the neurodegeneration seen in secondary progressive MS.
