Myostatin and Creatine/Creatinine Ratio Biomarkers Track Duchenne Muscular Dystrophy Progression

Monitoring disease progression in Duchenne Muscular Dystrophy (DMD), a severe muscle-wasting disorder, is challenging. Traditional functional tests are affected by patient age, variability, and motivation, while clinical milestones are often too slow for trial endpoints. There's a critical need for objective, reliable blood biomarkers that can reflect disease progression and evaluate treatment responses. This study investigated whether longitudinal changes in myostatin and creatine/creatinine ratio (Cr/Crn) could serve as such biomarkers, correlating with functional tests and key disease milestones.

Researchers conducted an observational study using longitudinal data from 74 DMD patients followed annually between 2009 and 2022. A total of 408 serum samples were collected over this period. Associations between log2-transformed biomarker levels (myostatin and Cr/Crn), functional tests (6-min walk test, North Star Ambulatory Assessment (NSAA), 10-m walk-run test velocity (10MWT), Performance of Upper Limb (PUL2.0)), and clinical milestones (loss of ambulation, overhead reach, hand-to-mouth function) were assessed using linear mixed models and time-dependent Cox models. A post-hoc sample size calculation also evaluated the biomarkers' potential to improve future clinical trial design due to lower intra-patient variability.

The study found significant associations between biomarker levels and disease progression in DMD patients. Lower Cr/Crn and higher myostatin levels were consistently associated with better functional performance and a less rapid decline in ambulation, independent of treatment and BMI. Specifically, children with one-unit higher log2-myostatin levels demonstrated, on average, 4.73 points higher NSAA and 3.40 points higher PUL2.0 scores, with both findings achieving high statistical significance (p-values < 0.001).