focus area: Causes and Prevention
funding type: Project
project type: Investigator Led Research
MS is a progressive disease that damages the brain and spinal cord, causing inflammation and loss of protective myelin around nerve cells. While treatments exist to manage early MS, options are very limited for people with progressive MS. Associate Professor Justin Rubio’s research aims to tackle a major hurdle that has slowed the development of therapies that could protect or repair the brain in progressive MS.
Associate Professor Rubio’s team has contributed significantly to understanding MS at the genetic level. Recently, they discovered that brain cells in MS lesions accumulate genetic mutations much faster than normal. This discovery suggests that certain genetic changes in the brain may influence how MS progresses. Their recent genetic study also suggest that how well the brains can adapt to damage, or their resilience, may play an important role in MS progression.
Building on these insights, Associate Professor Rubio and his team will use advanced methods to analyse genetic mutations, gene expression, and regulation in the brain. By combining these data with findings from their previous genetic study, they aim to identify genes and pathways involved in MS that could serve as targets for new treatments. The team will use computational tools to find these potential targets, drawing on public data as well as their expertise in MS research, from laboratory work to clinical application.
This project could pave the way for new therapies that protect brain cells and slow MS progression, offering hope for people with progressive MS.
Associate Professor Rubio and his team have made strong early progress in this project, refining their approach to better understand how genetic changes in the brain may drive progression in MS.
During the first year of the project, the team shifted their focus to study somatic mutations – genetic changes that occur within brain cells over time – in microglia, the brain’s immune cells. This adjustment was based on emerging evidence from related diseases suggesting that these mutations may contribute to harmful inflammation and ongoing damage.
To support this new direction, the team has successfully established methods to isolate microglia from human brain tissue with high accuracy. They implemented advanced laboratory techniques to confirm the purity of these cells and introduced a highly sensitive DNA sequencing approach that improves the detection of rare genetic mutations.
Early analyses of brain tissue have shown important differences in the types and frequency of genetic mutations present in microglia from areas of damage compared to tissue without damage. These differences were not detectable when analysing whole brain tissue, highlighting the value of focusing on specific cell types.
The team has also expanded access to additional brain tissue samples through collaboration with the MS Australia Brain Bank, allowing them to apply these methods to a larger number of cases.
This work has also contributed to further funding, with the team awarded an MS Australia Incubator Grant using methods developed in this project.
The project is now moving into the next phase, where the team will extend these analyses across more samples and further investigate how these mutations influence the behaviour of microglia.
This work is helping build a clearer understanding of how genetic changes within brain cells may drive disease progression, with the long‑term goal of identifying new drug targets for progressive MS.
Updated 31 March 2026Â
$249,958
2025
2 years
Current project
