Research we fund

A person’s genetics can influence their risk of developing MS. However, few MS genes have been identified, and it is not well understood how genes drive MS development.

Previous research by Dr Nicholas Blackburn and his team into the genetics of MS families (families that have 3 or more close relatives who have MS) has shown that there are genetic changes in MS families that may affect a person’s genes in a way that contributes to MS. These changes are rare in the general population but can occur multiple times in a single family because of shared genetics. These changes might be why some families have many people with MS.

The focus of this current project is to increase the number of MS families studied to establish if similar genetic changes to those already identified occur across other MS families. Dr Blackburn and his team will then use the genetic changes identified in MS families to test whether the same genes are linked to MS in data from thousands of people with MS. Together, this will provide clues as to why MS develops so strongly in some families and lead us to better understand why MS develops overall, including in people who do not have a family history.

Myelin is a protective, fatty layer that surrounds nerve cells and supports their function. In MS, myelin is damaged, and the cells responsible for making it, called oligodendrocytes, decrease in both number and effectiveness. A promising approach to treating MS is to encourage remyelination, by stimulating immature cells, known as oligodendrocyte precursor cells, to develop into mature oligodendrocytes that can regenerate this protective layer.

Mr Jack McDonald’s research focuses on a protein called GPR17, a type of receptor found in immature oligodendrocyte cells that have the potential to become myelin-producing cells. This receptor plays a crucial role in helping these cells mature, making it a potential target for drugs that could promote myelin repair in MS. While evidence suggests GPR17 could be effective in promoting remyelination, we still don’t fully understand how it works or how drugs might act on it.

Mr McDonald is studying the pathways affected by drugs targeting GPR17 to learn more about how this receptor contributes to myelin repair. Using genetic tools, drug-based methods, and advanced cell models, he aims to clarify GPR17’s role in remyelination. By uncovering how GPR17 influences myelin formation, Mr McDonald hopes to inform future drug development, not only for GPR17 but also for other receptors involved in the repair of myelin 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.

Extracellular vesicles (EVs) are particles with a lipid (fat) membrane that almost all types of cells release. EVs play an important role in travelling between cells as communicators and carrying a large range of substances that influence the biological functions of the receiving cells. EVs also have an effect on various disease processes.

EVs are hugely important in advancing our understanding of MS due to their role in communication between cells, their potential as non-invasive biomarkers (biological signs) and because they are able to cross the blood-brain barrier, a layer of cells that protects the brain from harmful substances. In MS, there is a great need to find reliable and non-invasive biomarkers and therapeutic targets.

PhD candidate Ms Drishya Mainali is travelling to Dr Magaña Setty’s laboratory at The Ohio State University for eight weeks to learn advanced techniques in isolating, characterising and analysing EVs. She will bring these techniques back to her laboratory at The University of Sydney, NSW and pass them on to her team. The techniques will also be used in ongoing research projects.

These advanced techniques are crucial for accurately profiling EVs in fluid samples from people living with MS. By enhancing her laboratory’s capabilities to profile EVs, Ms Mainali’s work will contribute to the early detection and monitoring of MS.

*For more details about the Ian Ballard Travel Award visit this page

Myelin is a key player in the correct functioning of nerve transmission. It surrounds nerve fibres like a sheath, protecting them and allowing the transmission of nerve messages between the brain, the spinal cord and the rest of the body. In MS, the myelin and the cells that produce it become damaged, causing the symptoms of MS.

Current disease modifying therapies (DMTs) do not directly repair myelin and are ineffective in treating progressive MS. Recently, a protein called GPR17 was found in brain cells responsible for generating the myelin sheath. GPR17 plays a critical role in the maturation and formation of myelin and activating GPR17 can stop the formation of myelin. Thus, blocking GPR17 is a new strategy to promote myelination in MS. However, current blocking molecules fall short as they only weakly block GPR17 and they also unintentionally block the activity of another protein, limiting their utility.

Dr Sheng Yu Ang and Dr Rocio de la Fuente Gonzalez aim to discover new molecules that will lay the foundation for the development of superior GPR17 blockers. They will run experiments on a chemical library to identify GPR17 blockers that can be developed into therapies to promote remyelination in people with MS.

In MS, the immune system mistakenly attacks the protective covering of nerve fibres in the brain and spinal cord (myelin), causing lesions (damaged areas).

Researchers have observed that, in addition to the inflammation caused when these lesions form, there is also slow, low-grade inflammation around the edges of older chronic lesions. This gradual inflammation contributes to the growth of lesions over time and is linked to disease progression, such as nerve damage, brain shrinkage, and worsening disability.

The researchers believe that this low-grade inflammation at the edges of chronic lesions could be an early sign of more localised inflammation in the brain. They think that promoting the repair of myelin (remyelination) could reduce this inflammation and stop the lesions from expanding, helping protect the nerves from further damage.

The study aims to test how effective remyelination therapies are in preventing damage caused by this slow-burning inflammation. The team will analyse data from clinical trials of remyelinating drugs to see if they can slow lesion expansion and prevent nerve damage.

By understanding how these therapies work and finding markers to measure their effectiveness, the researchers hope to develop better treatments for people with MS and improve their long-term outcomes.

MS is an autoimmune disease where immune cells attack the brain and spinal cord. Various immune cells have been implicated in this immune-mediated destruction; however their roles remain poorly understood. In addition, it is not fully understood how immune cells infiltrate the lesions and interact with each other.

One of the major challenges has been the lack of tools to help identify the various immune cells in tissues preserved for laboratory analysis. However, recent advances in tools have revolutionised the way these tissues can be studied and have led to the full mapping of cells and molecules. These maps show the types, locations, and interactions of cells and molecules.

Associate Professor Umaimainthan Palendira and Professor Georges Grau from The University of Sydney propose to map the cellular landscape of 10 MS brain lesions and 10 non-MS brain lesions, using these advanced tools. From this, we will better understand which immune cells are present within lesions and what cells they interact with or avoid within these lesions. The map may provide insights into the role of these cells and how they could contribute to the disease process.

We have known for years that exercise is beneficial for people with MS, yet most people with MS do not do enough exercise to experience these benefits.

Associate Professor Yvonne Learmonth and her team have found that people with MS, living in the UK, USA, Canada and Australia, would like to go to their doctors and nurses and discuss exercise, receive correct and consistent exercise information and receive tools or referrals to exercise specialists. They also found that doctors and nurses involved in MS care want to promote exercise to their patients, but they lacked the knowledge, strategies, resources and confidence to do this.

Associate Professor Learmonth and her team will listen to people with MS, and to doctors and nurses involved in MS care, to co-design an intervention and toolkit for MS healthcare providers to promote exercise to people with MS. They will ensure the intervention is based on established theory and principles so that it will resonate with people with MS. This approach will help people with MS achieve their exercise goals, learn skills to monitor their progress, feel good about mastering exercise and identify strategies to overcome barriers to incorporate exercise into their lives.

The team will design and test their intervention to ensure it can be implemented by doctors and nurses across MS care. At the end of the project, they will assess the ability of doctors and nurses to promote exercise and what impact this has on exercise behaviour in people with MS.