Progression of MS can at times be subtle and can be initially missed by doctors and patients alike. It is not uncommon that while MS may seem on the surface to be appropriately controlled, the condition is deteriorating quietly in the background. Once this silent deterioration manifests as worsening of disability, it is typically too late to reverse the loss of function.
This program revolves around detection, measurement and treatment of subtle progression of MS, especially amongst patients who are at the highest risk of silent deterioration of their disease. The project will first develop and validate a set of markers (clinical assessments, specialised investigations and biological markers) that will be sensitive enough to detect subtle changes in people with seemingly well-controlled MS. Second, it will develop a new method for monitoring the activity of the immune system within the brain. This method will first be validated in laboratory models and then translated to use in humans. Third, the program will develop a promising treatment for progressive MS called PEGylated-GAS6. This molecule modifies the behaviour of the immune system within the brain.
The completed research will set the scene for translating this treatment into a research program offered to people living with MS - a first-in-human randomised clinical trial of PEGylated-GAS6.
Professors Tomas Kalincik and Trevor Kilpatrick have secured funding from multiple sources to support the newly launched PRIMeS cohort in studying MS. The study protocol has been approved by sponsors, and the ethics and governance review are underway at the Royal Melbourne Hospital. Additionally, the launch of the RMH Neuroimmunology Centre is planned for August 2023, which will facilitate recruitment and follow-up of the PRIMeS cohort.
In addition, they have conducted studies on a lead candidate radioligand of MerTK (MER tyrosine kinase), a protein of interest in MS. The results show promising selectivity for MerTK and good binding within the brain. Further improvements are needed to enhance its utility as a marker for reparative immune brain cells called microglia. The team are working towards additional studies for validation.
They also focused on Gas6, a protein involved in remyelination. The research has demonstrated the importance of molecular changes in Gas6's remyelinative capacity. The study has also identified the short half-life of unmodified Gas6 in the brain and the potential benefits of PEGylation to increase its stability. Further work is needed to optimise PEGylation approaches.
These advancements hold potential for individualised therapeutic approaches and improved outcomes for people with 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. Epub 2021 Sep 4. PMID: 34563964.
Updated: 31 March 2023
Updated: 14 February, 2022
Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.
Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.
Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.