Mitigation of pathological parameters under Jagged1 influence in DMD knockout zebrafish and patient-derived myoblast cultures

Duchenne muscular dystrophy (DMD) is an X-linked, degenerative disease mainly affecting male children, with progressive weakness of whole-body skeletal muscles and the heart. There a gradual loss ambulation, heart weakness, breathing capacity by late teens. Heart or lung dysfunction causes early death in patients during second third decade. Steroid treatment delays progression 2-3 years, albeit serious side effects. The few FDA-approved gene therapies are mutation-specific exorbitantly priced. unmet medical need for children affected DMD. Interestingly, previous study showed that single nucleotide change caused Jagged1 overexpression, which resulted avoidance ambulatory 1-1.5-year-old golden retriever dogs severely dystrophy. Identifying pathological processes mitigated overexpression might help understand mechanism this rescue. Hence, we generated DMD knockout zebrafish, another severe model human (JAG1). Pathological aspects like cell death, proliferation, cytoplasmic mitochondrial oxidative stress were compared between dystrophic, rescued, control groups. Surprisingly, JAG1 increased rescue, while reducing other processes. Similarly, ROS production occurred Jag1 peptide vitro differentiated patient-derived myotubes, suggesting conserved involved