Key result
Urine and plasma titin fragment levels remained elevated in DYS-HAC1; DMD-null mice compared to wild-type mice, whereas plasma creatine kinase activity did not, indicating titin fragments are a more sensitive biomarker.
Why the study?
The difference in sensitivity between blood creatine kinase activity and urine titin fragment levels in monitoring DMD disease progression and evaluating therapeutic interventions remained unclear.
Are urine/plasma titin fragment levels a more sensitive biomarker than plasma CK activity in Duchenne muscular dystrophy model mice?
Are urine/plasma titin fragment levels a more sensitive biomarker than plasma CK activity in Duchenne muscular dystrophy model mice?
Urine and plasma titin fragment levels may serve as more sensitive biomarkers than plasma creatine kinase activity for monitoring disease progression and therapeutic efficacy in Duchenne muscular dystrophy.
Answers are grounded in this paper and cite their sources.
Titin fragments merit human validation studies in DMD; animal data leave open superiority to CK for monitoring.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations of the dystrophin gene, which spans 2.4 Mb on the X chromosome. Creatine kinase (CK) activity in blood and titin fragment levels in urine have been identified as biomarkers in DMD to monitor disease progression and evaluate therapeutic intervention. However, the difference in the sensitivity of these biomarkers in DMD remains unclear. Previously, we generated transchromosomic mice carrying the full-length human dystrophin gene on a human artificial chromosome (DYS-HAC1) vector. The human dystrophin derived from DYS-HAC1 improved pathological phenotypes observed in DMD-null mice, which lack the entire 2.4 Mb of the dystrophin gene. In this study, we compared the values of plasma CK activity and urine/plasma titin fragment levels in wild-type (WT), DYS-HAC1, DMD-null, and DYS-HAC1; DMD-null mice. Plasma CK activity and urine/plasma titin fragment levels in DMD-null mice were significantly higher than those in WT mice. Although plasma CK activity showed no significant difference between WT and DYS-HAC1; DMD-null mice, urine/plasma titin fragment levels in DYS-HAC1; DMD-null mice were higher than those in WT mice. Human dystrophin in DYS-HAC1; DMD-null mice drastically improved muscular dystrophy phenotypes seen in DMD-null mice; however, the proportion of myofibers with central nuclei in DYS-HAC1; DMD-null mice had a tendency to be slightly higher than that in WT mice. These results suggest that urine/plasma titin fragment levels could be a more sensitive biomarker than plasma CK activity.
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Hiramuki et al. (2025) studied Duchenne muscular dystrophy. DYS-HAC1 (human dystrophin gene on human artificial chromosome) vs. Wild-type and DMD-null mice was evaluated on Urine and plasma titin fragment levels versus plasma creatine kinase (CK) activity (p=<0.05). Urine and plasma titin fragment levels remained elevated in DYS-HAC1; DMD-null mice compared to wild-type mice, whereas plasma creatine kinase activity did not, indicating titin fragments are a more sensitive biomarker.
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