DrSamuel Klistorner

MS Australia Fellowship

Role: Chief Investigator A | Funder: MS Australia | Status: Active

Supports Samuel's independent research program on MRI biomarkers of smouldering inflammation in multiple sclerosis, including development and validation of the LEAP pipeline for chronic lesion tissue expansion (CLTE). The fellowship underpins his capacity to lead and grow an independent biomarker research program at the Brain and Mind Centre, University of Sydney.

Targeting Smouldering Inflammation in Multiple Sclerosis: Evaluating Treatment Effects with a Novel Biomarker

Role: Chief Investigator A | Funder: Medical Research Future Fund (MRFF EMCR Award) | Status: Active

A registry-enabled imaging biomarker study examining the effect of disease-modifying therapies on chronic lesion tissue expansion in MS. Using the MSBase international registry and longitudinal imaging data from Australian MS centres, this program applies the LEAP pipeline to characterise how different DMT mechanisms influence smouldering lesion activity over time. Findings are directly relevant to therapy selection and the design of future smouldering-targeted clinical trials.

MS Australia Project Grant - DMT Effects on Chronic Lesion Expansion

Role: Chief Investigator | Funder: MS Australia | Status: Active

Examines the relationship between therapy class and CLTE across a real-world MS cohort, using rigorous causal inference methods including propensity score matching and inverse probability of treatment weighting. This work investigates a distinct set of treatment comparisons from the MRFF EMCR program, generating registry-scale evidence on which therapeutic approaches most effectively suppress smouldering lesion pathology.

Investigator-Initiated Study - CLTE as a Biomarker of Therapeutic Response

Role: Chief Investigator | Funder: Merck (industry partnership) | Status: Complete

An investigator-initiated analysis funded by Merck examining chronic lesion tissue expansion across four DMT groups (cladribine, ocrelizumab, fingolimod, natalizumab) in 201 patients across four Australian centres. This work applied multivariable regression, propensity score matching, and IPTW to characterise treatment-specific effects on smouldering lesion pathology, with translational relevance for drug development and label expansion.

Visual System Biomarkers for Monitoring Chronic Inflammation in Multiple Sclerosis

Role: Co-Investigator | Funder: Australian Vision Research (AVR Grants Program) | Status: Active

This project leverages the visual system as a model for studying smouldering neuroinflammation in MS. The optic radiation, periventricular in location and frequently affected by MS lesions, represents an optimal site to study chronic active lesion pathology. The study applies the LEAP pipeline to quantify chronic lesion tissue expansion within optic radiation lesions in a longitudinal cohort of 150 RRMS patients with up to 7 years of annual MRI, multifocal visual evoked potential (mfVEP), and optical coherence tomography (OCT) data. Aims include determining whether progressive mfVEP changes track smouldering lesion activity within the optic radiation, and whether retrograde trans-synaptic degeneration detectable by OCT serves as a distal readout of ongoing perilesional inflammation. This work positions CLTE within a multimodal visual biomarker framework and establishes proof-of-concept for a subsequent NHMRC-funded validation study.

A Novel Registry-Based Trial Targeting Chronic Inflammation in the Brain

Role: Co-Investigator (Imaging Analysis Lead, LEAP Implementation) | Funder: Under embargo | Status: Active

This project builds a registry-based clinical trial infrastructure to evaluate whether current MS therapies differ in their ability to suppress smouldering inflammation, using CLTE as the primary imaging outcome. The study emulates a randomised trial design using real-world clinical and MRI data from the MSBase Registry and MSBase Imaging Repository (MSBIR), together encompassing over 120,000 patients across 205 centres in 45 countries and more than 50,000 linked MRI scans. Data are structured into Treatment Epochs representing stable, continuous exposures to individual DMTs, enabling causal inference via propensity score weighting and generalised linear modelling across 1,200 epochs from eight DMT classes. Samuel leads LEAP deployment and imaging biomarker analysis across the registry dataset, integrating CLTE quantification with the iQ-MS AI lesion segmentation platform. This infrastructure represents the first large-scale, registry-enabled head-to-head comparison of treatment effects on smouldering inflammation, with direct relevance to clinical guideline development and PBS policy.

Note: Full award details subject to embargo; enquiries welcome.