Being able to correctly monitor the level of MS activity is always important in clinical care, but particularly so during a clinical drug trial where the ability for a new drug to stop MS activity is being assessed. Currently, monitoring progression of MS over time in clinical trials is challenging and there is no one test which can accurately make that assessment.
We currently know that as MS progresses, inflammatory cells within the brain called microglia are active, and likely to be contributing to disease progression over time. However, there are different types of microglia, pathogenic (indicating active disease) and reparative (indicating a repairing phase and less disease activity). At present, there is no way to distinguish between the two types of microglia to measure the microglial response and to know if MS progression is occurring.
Dr Vivash and her team aim to develop techniques to identify both the extent and the nature of this microglial response. They plan on doing this by developing a new compound to be used in a non-invasive PET (positron emission tomography) scan to determine the level of disease activity and MS progression. This could help fill an unmet need in clinical trials for new MS drugs by helping to identify effective drugs to treat progressive MS sooner and more accurately.
Over the past year, Dr Vivash and her team have made significant progress in developing new compounds for PET brain imaging aimed at improving the diagnosis of MS. Their work focused on refining the chemical structure of tracer compounds to ensure they could enter the brain more easily and stay long enough to be useful for imaging, addressing a key limitation in earlier versions that cleared too quickly.
Through this process, the team created and tested a third generation of compounds, identifying several with improved imaging potential. They also enhanced their laboratory models to better assess these compounds, including methods to increase the visibility of the target protein in the brain. This helped identify which compound properties are most important and which tests best predict success.
While the original goal of producing a clinically ready imaging agent for MS was not achieved, the project has delivered critical insights. The team now has a clear understanding of how to optimise future compounds, and which changes are most likely to improve their effectiveness.
With support exceeding $2 million AUD, including funding from the Department of Industry, Science, Energy and Resources (DISER), Australia, and the US National Institutes of Health, and strengthened by new international collaborations, this project has laid valuable groundwork for future innovation. The knowledge gained represents an important step toward improving imaging tools and deepening our understanding of MS.
Wong SW, Vivash L, Mudududdla R, Nguyen N, Hermans SJ, Shackleford DM, Field J, Xue L, Aprico A, Hancock NC, Haskali M, Stashko MA, Frye SV, Wang X, Binder MD, Ackermann U, Parker MW, Kilpatrick TJ, Baell JB. Development of [18F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease. Eur J Med Chem. 2021 Dec 15;226:113822. doi: 10.1016/j.ejmech.2021.113822.
Updated 31 March 2025
$235,000
2021
3 years
Current project
