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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 people 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 for 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 Progression in Multiple Sclerosis (PRIMeS) cohort in studying MS. The study protocol has been approved by sponsors, and has received ethics approval from the Royal Melbourne Hospital (RMH) Human Research Ethics Committee and is the final stages of governance approval.
In October 2023, the RMH Neuroimmunology Centre was launched. It is the first neuroimmunology centre of its kind in Australia, with permanent allocation of space, staff, and resources by a tertiary public hospital. This enables integration of clinical activities, clinical research, educational activities and consumer engagement at a single location.
With the launch of the neuroimmunology centre, recruiting into and follow-up of the PRIMeS participant cohort is expected to commence shortly.
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. This candidate molecule is a promising marker of reparative microglia (an immune cell of the central nervous system), depending on validation of the results.
They also focused on Gas6, a protein involved in myelin repair (remyelination). The research has demonstrated the importance of molecular changes in Gas6’s remyelination capacity. The study also identified that the half-life of unmodified Gas6 within the brain is less than 20 minutes. In contrast, PEGylated Gas6 is still detectable 4 hours later, highlighting the potential benefits of PEGylation to increase its stability. Further work is needed to optimise PEGylation approaches.
These advancements hold potential for individualised treatment approaches and improved outcomes for people with MS.
Professors Kalincik and Kilpatrick have submitted a patent application for this work and have also received extra funding from two industry partners and a private donor.
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. Top of FormÂ
Updated 31 March 2024
$750,000
2022
3 years
Current project
