Limitations of Current Treatments for Chronic Active Lesions
Current disease-modifying therapies (DMTs) show limited effectiveness in treating chronic active lesions (CALs), a key driver of MS progression. Despite advances in MS treatment, CALs present unique challenges due to their distinct pathological features, including sustained microglial activation, iron-mediated tissue damage, and compartmentalized inflammation.
High-efficacy anti-inflammatory treatments have shown inconsistent results in targeting CALs. Even powerful B-cell depleting therapies like ocrelizumab demonstrated limited impact on chronic lesion activity in progressive MS. Traditional DMTs struggle to address the compartmentalized inflammation within CALs, where the blood-brain barrier often remains intact, limiting drug penetration and effectiveness.
Some newer therapies show early promise, with ibudilast reducing slowly expanding lesion activity and evobrutinib showing reduction in lesion volume. Traditional agents like natalizumab and fingolimod demonstrate limited effects. However, measuring these treatment effects has been challenging due to limitations in quantifying lesion changes.
Advancing Treatment Assessment with LEAP
The Lesion Expansion and Analysis Pipeline (LEAP) represents a significant advance in measuring chronic lesion activity. This technique enables precise quantification of lesion expansion and reliable assessment of treatment effects through a standardized measurement protocol suitable for clinical trial implementation. The methodology allows for more accurate evaluation of treatment efficacy and shorter trial durations, enhancing our ability to identify promising treatments and validate DMT effectiveness.
This advancement in measurement methodology streamlines drug development and validation, potentially accelerating the path to effective CAL treatments.
We designed COMPASS-MS, a pioneering international study comparing the effectiveness of different disease-modifying therapies on smouldering inflammation. Using our LEAP methodology across multiple international centers, this multi-center investigation analyzes existing patient data to establish the first comprehensive comparison of current treatments.
We developed a novel approach to clinical trials focusing on smouldering inflammation, showing how chronic lesion expansion can serve as a powerful and efficient endpoint. Our research demonstrates that meaningful treatment effects can be detected with smaller patient groups, creating new opportunities for evaluating targeted therapies while maintaining robust scientific standards.
MS Lesion Analytics 