Author(s): GOLDFARB, I., YANAY, N., RABINOWITZ, R., HOREV, R., NEVO, Y., AHARONI, S., RABIE, M., MOSS, T., SHNAYDERMAN, T., TAIZI, T., BARAZANI, C., SHOCHAT, T., CONSTANTINI, N., NEVO, Y., Institution: KAYE ACADEMIC COLLEGE OF EDUCATION, Country: ISRAEL, Abstract-ID: 1120

INTRODUCTION:
Children with Duchenne and Becker muscular dystrophies (DMD/BMD) are characterized by progressive muscle weakness, yet concerns about exercise-induced muscle damage often limit engagement in physical activity. Plasma microRNAs (miRNAs) offer a sensitive tool for detecting muscle injury and effort adaptive responses, but data regarding miRNAs response following light aerobic training in dystrophinopathies is limited. The aim of this study was to evaluate pre- and post-training miRNA responses of 12-week light aerobic program in children with dystrophinopathies.
METHODS:
Thirty children (DMD n=10, BMD n=10, controls n=10) completed a 12-week remote light-aerobic training program. Plasma miRNAs were collected before and after the training period, sequenced on an Illumina NextSeq 500, and analyzed using a standardized pipeline for trimming, UMI-based deduplication, alignment to miRBase v22, and differential expression testing in DESeq2 (padj < 0.1).
Functional assessments included the 6MWT, NSAA, hand-held dynamometry, and serum CPK. Between-group comparisons used ANOVA or Kruskal–Wallis tests, and pre-post changes were assessed and analyzed using paired t-tests or Wilcoxon tests (p ≤ 0.05).
RESULTS:
At baseline, DMD and BMD showed distinct miRNA signatures compared with controls, primarily involving myomiRs, myogenesis, mitochondrial biogenesis, and inflammatory pathways. After training none of the miRNAs associated with muscle degeneration were elevated in these children. After 12 weeks, 26 miRNAs showed significant changes in children with BMD consistent with positive exercise adaptation, including markers of muscle regeneration (e.g., miR-16-2-3p, hsa-miR-451a, hsa-miR-363-3p, has-miR-1, hsa-hsa-miR-143-3p, hsa-miR-27b-3p, hsa-miR-379-5p, hsa-miR-199a-3p and hsa-miR-99b-5p), mitochondrial biogenesis (miR-28-3p, miR-146a-5p), and anti-inflammatory signaling (has-miR-4580, hsa-miR-223-5p, hsa-miR-134-5p, hsa-miR-139-5p, hsa-miR-409-3p, hsa-miR-340-3p, has-miR-432-5p, has-miR-1277-5p, and has-miR-12136). In children with DMD, hsa-miR-133a-5p, hsa-miR-206, hsa-miR-378a-5p, miR-744-5p, and hsa-miR-4508 miRNAs demonstrated similar non-significant trends.
Functionally, physical activity adherence was high across groups during the study period, with DMD completing shorter and slower sessions but demonstrating comparable cardiovascular responses. Functional capacity remained stable over 12 weeks (6MWT, NSAA, quadriceps; all p>0.05), while hamstring strength improved in both DMD (p=0.045) and BMD (p=0.02). CPK levels and exertional CPK ratios remained unchanged, reinforcing training safety.
CONCLUSION:
These findings suggest that short term light aerobic training is feasible, safe, and elicits beneficial molecular adaptations in children with dystrophinopathies.