The Mechanisms of Axonal Degeneration in Multiple Sclerosis (MAD-MS) study represents a landmark research initiative that has transformed our understanding of how MS progresses over time. This comprehensive research program, generously supported by the National Multiple Sclerosis Society (NMSS), has yielded crucial insights into the subtle yet significant ways MS affects the brain, particularly in periods between relapses.
A Decade of Discovery
Over the past decade, our team followed 200 people living with relapsing-remitting MS, most for five or more years. This extensive commitment from our participants has enabled us to build one of the most detailed pictures yet of how MS evolves over time. Through annual clinical assessments and advanced brain imaging, we’ve uncovered critical new information about disease progression that occurs independently of relapses – what we call “silent” progression.
Major Breakthroughs
Our research has led to several groundbreaking discoveries that are changing how we think about MS:
Perhaps our most significant achievement has been revealing how chronic MS lesions slowly expand over time due to persistent, low-grade inflammation at their edges. We developed new methods to accurately measure this expansion and showed that it significantly contributes to brain tissue loss and disability progression. This work has opened new avenues for developing targeted treatments.
Our research has uncovered an exciting new frontier in MS research – the role of the choroid plexus. This specialized brain structure, which produces cerebrospinal fluid, shows significant changes in people with MS. We discovered that choroid plexus inflammation and enlargement correlates strongly with disease progression and lesion expansion, particularly in progressive forms of MS. This breakthrough finding suggests the choroid plexus could serve as a valuable biomarker for monitoring disease activity and treatment response.
Using the visual system as a window into MS progression, we provided the first human evidence that chronic demyelination (long-term loss of myelin) directly promotes nerve fiber loss. This finding makes a compelling case for developing new therapies focused on remyelination – helping the brain repair damaged myelin coating around nerve fibers.
Impact and Future Directions
The data collected as part of the MAD-MS study continues to drive innovation in MS research and treatment. Our most exciting development is the design of COMPASS-MS (Comparing Outcomes of Multiple Pharmacotherapies on Active Smouldering Sites in MS), a groundbreaking international clinical trial proposal built upon the measurement tools and insights we developed through MAD-MS. This world-first investigation will compare how different MS treatments affect smoldering inflammation in chronic lesions – a critical factor in disease progression we identified through MAD-MS. By leveraging patient data from multiple international centers, COMPASS-MS has been designed to deliver crucial insights within 18 months that could transform treatment selection for people with MS.
Furthermore, we recently expanded the study by adding a cohort of Progressive MS patients. Discoveries from the MAD-MS study have been published in 36 papers in leading medical journals, including Brain, Lancet Neurology, Annals of Neurology, Multiple Sclerosis Journal. More importantly, our findings are already shaping clinical trials and treatment approaches. The tools and methods we developed are now being used worldwide to test new therapies and monitor disease progression more effectively.
To our study participants: your dedication to this research has been instrumental in advancing our understanding of MS. Your commitment has helped establish:
- New ways to measure disease progression
- Better understanding of how MS affects brain tissue over time
- More precise methods for testing new treatments
- Clear evidence for the importance of early intervention in MS
The MADMS study stands as a testament to the power of long-term research and the vital partnership between researchers and people living with MS. Together, we have build the foundation for a more comprehensive insight into MS, paving the way for more effective treatments and, ultimately, better outcomes for everyone affected by the disease.
MS Lesion Analytics 