I completed my ophthalmology training in Russia in 1985 and later earned a PhD from the University of New South Wales in 1996. I got involved in multiple sclerosis (MS) research in 2008, when I conducted a pioneering study on the structure-function relationship in the visual systems of patients with optic neuritis. Later I also led studies on optic nerve remyelination, which have become benchmarks for MS therapy trials. I have also been involved in international clinical trials as both an investigator and study designer. I have secured over $6 million in research funding, including grants from the National Multiple Sclerosis Society (USA) and the National Health and Medical Research Council (NHMRC). My collaborations span institutions in Germany, Israel, Italy, Spain, and Canada, reflecting my commitment to global research partnerships.

My involvement in MS research is attributed to my background in ophthalmology and neurology, where the visual system plays a significant role. MS often affects the optic nerve, leading to vision-related symptoms, which naturally aligns with my expertise in visual system disorders. My early work with optic neuritis – an inflammation of the optic nerve common in MS – sparked a deeper interest in understanding and addressing the neurological and visual impacts of MS.

Apart from the development of new therapies addressing disease progression (such as BTK inhibitors), the first adaptive clinical trial in MS in Australia, PLATYPUS (PLatform Adaptive Trial for remYelination and neuroProtection in mUltiple Sclerosis), targeting progressive MS, represents another major innovation. This trial design allows simultaneous testing of multiple treatments, aiming to expedite the discovery of effective therapies for progressive MS.

The low-grade inflammatory demyelination at the edge of chronic MS lesions has been implicated as a major factor contributing to disease evolution. Ongoing myelin breakdown in the periplaque white matter of chronic lesions is established in pathology and imaging studies. Experimental evidence also suggests that permanent demyelination causes axonal damage by rendering axons vulnerable to physiological stress. Therefore, prevention of myelin damage and promotion of myelin repair is considered the most potent strategy to prevent axonal degeneration and slow down disease progression. However, all remyelination trials up to date have concentrated on remyelination of chronically demyelinated brain tissue. We recently presented first data showing that loss of myelin represents an initial step in a chain of events leading to compartmentalised inflammation around chronic MS lesion.

We hypothesised that early application of remyelinating therapy may potentially prevent neurodegeneration caused by slow-burning inflammatory demyelination, providing, therefore, significant clinical benefit. We plan to investigate the potential effect of remyelinating therapies in preventing damage to brain tissue around chronic MS lesions using real-life data from five Phase 2 treatment trials of remyelinating agents.

We will estimate the predictive power of MRI-based biomarkers of demyelination (such as Radial Diffusivity and Magnetisation Transfer Ratio) in the perilesional white matter of chronic lesions on future lesion expansion. Furthermore, factors associated with a decreased rate of chronic lesion expansion, such as central brain atrophy and longitudinal changes of MD and MTR in the lesion core will be explored as potential surrogate biomarkers of the efficacy of treatment.

The relationship between acute inflammation, compartmentalised inflammation, and neurodegeneration needs to be better understood to allow more precise intervention and the development of new therapeutic approaches.

The proposed study addresses the need to investigate the potential role of remyelination in preventing brain damage caused by low-grade inflammation at the rim of chronic MS lesions. By exploring the effectiveness of early application of remyelinating therapies in halting neurodegeneration associated with slow-burning inflammatory demyelination, the study aims to advance our understanding of disease progression and identify potential therapeutic strategies.

The study focuses on real-life data from five Phase 2 treatment trials of remyelinating agents. By analysing the outcomes of these trials, the study aims to provide valuable insights into the efficacy of remyelinating therapies in preventing damage to brain tissue around chronic MS lesions.

Furthermore, the study aims to identify MRI-based biomarkers of demyelination in the perilesional white matter of chronic lesions that can predict future lesion expansion. By exploring factors associated with decreased chronic lesion expansion, such as central brain atrophy and longitudinal changes in diffusivity and magnetisation transfer ratio, the study seeks to establish surrogate biomarkers for treatment efficacy.

The impact of the study is expected to be significant. It will enhance our understanding of the pathophysiology of compartmentalised inflammation in MS and its role in disease progression. The establishment of new biomarkers for monitoring compartmentalised inflammation will have practical implications in clinical settings, enabling clinicians to assess disease activity and predict disease progression. This personalised approach to treatment assignment will optimise patient outcomes and improve long-term prognosis.

Moreover, the study has the potential to revolutionise the therapeutic landscape for progressive MS. If it demonstrates that repairing or preventing myelin loss at the rim of chronic active lesions can slow down disease progression, it will pave the way for the development of targeted therapies for the progressive stage of the disease.

I do find satisfaction in the potential impact of my research on improving diagnostic tools and treatment approaches for MS, particularly as my work addresses a challenging and complex disease with profound effects on patients’ lives. The process of uncovering insights that could influence clinical practices and help slow or prevent disease progression is very rewarding.

On the challenging side, managing the technical and methodological complexities of imaging biomarkers in MS research is demanding. Balancing the need for precision and innovation with limited resources and strict timelines in grant-funded projects also presents a challenge. Furthermore, communicating the nuances of my findings to the scientific community while ensuring the clinical relevance of my research is demanding.