A newly published study led by CMTA’s Strategy to Accelerate Research (CMTA-STAR) Clinical Expert Board Co-Chair Professor Mary M. Reilly, MBE, MD, and colleagues explores how MRI can track disease progression in CMT1A and serve as a potential biomarker for clinical trials.
The study, Longitudinal MRI Study in CMT1A: One-Year Changes Predict Long-Term Progression, followed 20 individuals with CMT1A over four years and found that MRI-based muscle fat measurements taken just 12 months after the initial scan correlated with long-term symptom worsening.
These findings suggest that MRI could provide an earlier and more reliable way to track CMT1A progression compared to traditional clinical tests, helping to speed up clinical trials and the development of potential treatments.
Using MRI to Track Disease Progression in CMT1A
One of the biggest challenges in CMT1A research is that the disease progresses slowly. This makes it difficult to measure change over short periods, creating a major hurdle for clinical trials. Most trials rely on functional assessments like the CMT Examination Score (CMTES) to determine whether a treatment works, which might not be sensitive enough to show changes in a short period.
Professor Reilly and colleagues show that MRI fat fraction analysis, which measures how much muscle is replaced by fat as muscles weaken and atrophy over time, could provide a more sensitive way to track disease progression.
The study found that:
- Muscle fat increased steadily in people with CMT1A over four years, while healthy controls had little to no change.
- Changes in MRI at just 12 months correlated with clinical decline over four years, showing that MRI can detect disease progression much earlier than traditional measures.
- These findings suggest that MRI could be a valuable tool for measuring disease progression in shorter timeframes, making it useful for clinical trials.
How Can MRI Speed Up Clinical Trials?
The study also found that not all CMT1A patients experience muscle fat accumulation at the same rate as muscles weaken from the effects of CMT. This is important for clinical trials because it helps researchers understand where disease progression is most measurable.
- People with moderate muscle fat at the start of the study (5–70 percent) showed the most change over time.
- People with very advanced CMT (more than 70 percent fat in their muscles) had little additional fat accumulation, meaning MRI was less useful for tracking progression in these cases.
These findings suggest that MRI could help researchers design more efficient clinical trials by identifying where disease progression is most measurable. A clearer understanding of how CMT1A progresses in different individuals may lead to better trial designs, improving the chances of detecting treatment effects.
A Potential New Biomarker for CMT1A
Professor Reilly and her team’s findings support MRI as a possible new biomarker for measuring disease progression in CMT1A.
This could:
- Provide a more accurate way to track CMT1A progression
- Make clinical trials faster and require fewer participants
- Help researchers evaluate potential treatments more efficiently
While more research is needed, ongoing studies like the CMTA-supported ACT-CMT extension study will help confirm these findings. If validated, MRI could become a key tool for testing future treatments for CMT1A.
Looking Ahead: What This Means for the CMT Community
Professor Reilly and colleagues emphasize that MRI technology can potentially transform how CMT1A research is conducted. MRI could help bring new potential treatments to clinical trials sooner and, ultimately, to the community by providing a faster, more precise way to measure disease progression.
Professor Reilly’s paper is published in Annals of Clinical and Translational Neurology, where you can read it in its entirety.
Published on: April 24, 2025