Commencing January 2022, Dr Izanne Roos was awarded a 3-year Trish Translational Research Project Grant titled, “Personalised therapy to prevent disability in aggressive multiple sclerosis”.

In this Research Project Dr Roos is aiming to validate statistical models which can predict an individual’s risk of developing eight key multiple sclerosis milestones. She will then establish whether early use of the most potent therapies can improve disease outcomes in those patients at high risk of aggressive forms of multiple sclerosis.

Dr Roos is using data from big MS registries (MSBase, an international registry and OFSEP, the French National registry), utilising cohorts of patients living with MS from Barcelona and Melbourne from early after MS onset.  Dr Roos and her team have successfully validated a prognostic model developed in Barcelona that creates an individualised prediction model for the 10-year risk of eight relevant milestones (relapses, MRI activity and disability accumulation). This can be used in future to gauge an individual’s future risk of disease severity.

Dr Roos and her team have studied the effectiveness of high-efficacy therapies in people with MS at the highest (and lowest) risk of developing disability. They have found that high-efficacy therapy reduces risk of relapse and disability accumulation in all patients, irrespective of their risk of aggressive MS. This emphasises the importance of high-efficacy therapy in improving outcomes in people with MS.

There were seven publications during the year showing expertise in the analysis and interpretation of observational data.  Manuscripts are in preparation and Conference presentations will be submitted for 2024 ECTRIMS, the world’s largest MS Research Congress which attracts an estimated 9,000 delegates from all corners of the world.

Subsequent analyses will directly explore the timing of high-efficacy therapy on disease outcomes and we look forward to hearing of Dr Roos’ continuing progress with this important work.

Having been awarded a 3-year Trish Translational Research Project Grant titled, “Advancing tolerogenic dendritic cell therapy for multiple sclerosis toward clinical translation” which commenced January 2023, Professor Trevor Kilpatrick and Dr Vivien Li are making significant progress.   They are working on a new way to treat MS, based on using patients’ own blood immune cells.  These immune cells are treated with anti-inflammatory signals in the laboratory and then re-administered to the patient where they selectively target and dampen down the disease-causing immune cells that promote inflammation and lead to nerve cell damage in MS. This approach has benefits over existing therapies as it targets key initiating events in MS and could treat all disease stages. The targeted cells can cross into the central nervous system to dampen down disease-causing immune cells that are otherwise hidden from current treatments.

The team has already developed techniques to grow these immune cells from patient blood samples and defined culture conditions that can modify their behaviour to assume protective/anti-inflammatory rather than disease-inducing/pro-inflammatory characteristics. They have identified a relevant peptide involved in MS which can enable selective targeting of the disease-causing immune cells rather than broadly suppressing the immune system. Using advanced immunological techniques, they have found that frequency of immune cells that react to the identified peptide is higher in patients with MS compared to healthy controls. Furthermore, there was a higher proportion of cells with disease-inducing/pro-inflammatory characteristics. These findings further support the relevance of this peptide.

Professor Kilpatrick’s and Dr Li’s project will advance their existing work towards clinical translation.  They have established a partnership with Cell Therapies to facilitate development of tolerogenic dendritic cells towards clinical trial.  After only the first year of their 3-year Trish Translational Research Project, they have published a manuscript in the International Journal of Molecular Sciences and have another manuscript under review for the Journal of Neuroimmunology.  As well, an oral platform presentation has been selected for the ANZAN Annual Scientific Meeting 2024.

Commencing January 2020, Dr Steven Petratos, Monash University, was awarded a 3-year Trish Translational Research Project Grant titled, “Developing a new drug to repair the brain in Multiple Sclerosis”.

Dr Petratos and his team have been looking to repurpose a drug previously approved for use in a different neurological condition.  He had previously shown that this drug may slow the progression of MS in a laboratory model of MS.

Despite the disruptions and challenges caused by COVID early in his work, Dr Petratos has made exceptional progress.

Dr Petratos and his group uncovered that in the brains of individuals living with progressive MS, there are protein changes that cause the death of brain cells. These proteins are in the cells that produce myelin. Importantly, the group has uncovered that a new class of medicines, known as small molecules, can access the brain to stop the death of these brain cells by protecting these proteins. This outcome has major implications in the protection of the myelin forming cells in the brain and can limit further damage imposed by the immune attack as seen in the progression of MS. Dr Petratos has been investigating whether the drug can also reverse the damage to the brain by activating stem cells to become myelin-forming cells. In experiments with the animal model of MS, his team has now shown that the drug can repair the damaged myelin through a process known as remyelination. These outcomes will allow entry into a future Phase 2 clinical trial in Australia to stop and reverse the damage to the brain that occurs in progressive MS. A service agreement has been now entered into with Monash University and the commercial company NeuOrphan Pty Ltd that will progress this drug toward the Clinical Trials.

Dr Petratos and his team have been collaborating with researchers at the University of Tasmania trialling the MCT-8-independent thyroid hormone analogue DITPA, as a potential therapeutic agent in demyelination to promote protection and repair of the brain during the immune attack against myelin. He is also the holder of a patent for the use of this drug for neurological conditions that has been granted in Australia, US, Canada and Europe.

The repurposing of the drug DITPA may have the potential to become a “first-in-class” therapeutic for individuals living with MS if clinical trials demonstrate that it can protect and potentially repair areas of the brain, spinal cord and optic nerve that have been damaged due to the disease. With further commercial funding on the horizon, this work will promote the development of potential “best-in-class” therapeutics that may promote substantial pharmaceutical industry interest in a series of new medications formulated for protection and repair of the brain during MS.

The Trish Foundation is proud and honoured to be contributing to the ground-breaking work of Dr Petratos, having first funded his research in our inaugural round of funding in 2002.

Dr Petratos, working with Professor Paul Stupple, The Monash Institute of Pharmaceutical Sciences, has been awarded a 2-year Trish Translational Research Project Grant commencing January 2023 titled, “Development of Small Molecules to Promote Remyelination in Multiple Sclerosis”.  The Foundation’s volunteer team and our generous Sponsors and donors look forward to learning of more advancement of Dr Petratos’ promising research.

Commencing January 2020, Dr Vivien Li, The Florey Institute of Neuroscience and Mental Health Victoria, was awarded a Postgraduate Research Scholarship over three years funded by the National Health & Medical Research Council with ‘top up’ funding provided by the Trish MS Research Foundation.  The aim of the Project titled, “Towards developing dendritic cell therapy for multiple sclerosis based on promoting Mertk signalling” was to study ways to dampen down the abnormal immune activation, which would hopefully lead to new ways of combatting MS.

Despite being delayed by Covid, with laboratory access being reduced early in her work, Dr Li made good progress, including collection of blood samples from patients with MS; exploring the effects of tolerogenic factors dexamethasone and vitamin D3 on expression of Mertk and other cell surface markers on dendritic cells; testing different protocols, including serum-free conditions for differentiation of monocytes into dendritic cells with good viability and with tolerogenic potential.

Dr Li has been granted a 6-month extension by the NHMRC for COVID-19 related delays and her Postgraduate Scholarship is now being continued until September 2023.

Commencing January 2019, Dr Junhua Xiao, the University of Melbourne, was awarded a 3-year Project Grant titled “How neurons regulate cortical and subcortical remyelination”.  Dr Xiao subsequently left the University and her Project Grant was awarded to A/Prof Simon Murray who has continued her important work.

In this research the scientists have been looking at a protein called TrkB which is made in the nerve cells in the brain and seems to be important in the remyelination process.  Using a combination of ground-breaking scientific approaches, the project has been looking at what happens to the remyelination process in cells in the presence and absence of TrkB.

A/Prof Murray has sent the following report:

“This grant has continued to progress well.  We have used an experimental model of central nervous system demyelination to dissect the role that a molecule, called TrkB, exerts upon myelin repair.  We have been working on the TrkB molecule for some time and we believe it holds promise as a therapeutic target for repair in MS.  In these particular experiments, we interrogated the role that TrkB expressed on nerve cells exert upon myelin repair.  After extensive analysis of a number of experimental cohorts, the data are clearly demonstrating that neuronal TrkB exerts little effect upon myelin repair.  These data were not as expected and quite surprising, but is nevertheless an important finding and has helped us refine our hypotheses for future experiments and proposals.  I would like to acknowledge a PhD student in the lab, Ms Sangwon Yoo, for undertaking some of these analyses.  These experiments have formed a substantial part of her PhD thesis which we hope to submit by the end of this year.

This grant had an additional component that examined the nature of the interaction between oligodendrocytes and the nerves they myelinate.  Intriguingly, we are finding that the TrkB molecule is exerting significant differences in the way the oligodendrocytes make initial contact with axons.  This is novel and we are continuing to examine this.  This is all the more intriguing, as despite these differences in the initial contact, myelin repair appears to proceed unimpeded.

Finally, I would just like to add that grants such as these are extremely important to the lab, they really help us keep together in a very tight funding environment.  On the up-side, I am very pleased to let you know that the lab received a 5 year, $1.1M NHMRC Ideas Grant to continue our MS research.  This was announced at the end of 2021 and came into effect this year.  This new Ideas Grant is related to the work undertaken in the Trish grant, still focussing our attention on TrkB in remyelination.  So we are grateful for the time and effort you, your Foundation and your donor groups put in, they really help the lab along.”

Due to the pandemic, a revised completion date to 31st December 2022 for A/Prof Murray’s Project Grant was requested and approved.