Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. It is characterised by the development of lesions or spots of inflammation in the brain. While existing treatments radically reduce the risk of new lesions forming, they do not fully stop disease progression, suggesting that different disease activities are going on in the brain and spinal cord.
Clinical studies suggest that multiple mechanisms are implicated in the progression of the disease, particularly when MS progresses into secondary progressive MS (SPMS). It was suggested that chronic inflammation may make some of the nerve fibres more vulnerable to physiological stress. In addition to the damage at the site of lesions, these spots may induce damage in regions of the brain that are further away. However, clinical studies evaluating the role of these in progression of physical and cognitive disability in people with SPMS are lacking.
Therefore, the primary objective of the current project is to establish the role and predictive power of chronic lesions, “slow burning” inflammation and degeneration in progression of secondary progressive MS (SPMS). The research will use state-of-the-art neuroimaging techniques, partly developed in Professor Alexander Klistorner’s lab, to examine disease progression.
Professor Klistorner and his team have completed recruitment and follow‑up for this study, generating a large, detailed dataset of brain imaging collected over time in people with MS. This has enabled the team to investigate how MS changes the brain over time and contributes to disability progression.
A key outcome of the project is the finding that some MS lesions continue to slowly expand over time. This growth within existing lesions was shown to be a major contributor to ongoing changes to the brain and is strongly linked to brain volume loss and worsening disability. In many cases, this process contributes more to overall damage than the formation of new lesions.
Importantly, the research demonstrated that this slow, ongoing damage persists even in later stages of the disease, including secondary progressive MS. This challenges the traditional view that progression occurs independently of inflammation, showing instead that low‑level, ongoing inflammation within existing lesions continues to drive disease progression.
The project also showed that this type of damage can be measured reliably over time using MRI. This establishes chronic lesion expansion as a promising marker of disease progression that could be used to monitor MS and assess the effectiveness of new treatments.
In addition, the study improved understanding of other brain changes associated with MS. The team found that enlargement of a structure called the choroid plexus is linked to ongoing damage and brain volume loss, suggesting it may play a role in maintaining inflammation in the brain. The research also clarified the meaning of certain MRI features, showing that some markers previously thought to indicate active inflammation are more closely related to lesion size and age.
Overall, this project has provided new insights into the mechanisms driving long‑term progression in MS. It highlights the importance of slow, ongoing damage within existing lesions and provides practical tools to measure this process. These findings look towards better monitoring of progression both in clinical practice, as well as in clinical trials to support the development of therapies aimed at slowing or preventing long‑term disability.
Updated 31 March 2026
$642,000
2022
3 years
Past project
