2026-06-05 | Gene editing restores full-length dystrophin and affects iron homeostasis in hiPSC-derived cardiomyocytes from Becker Muscular Dystrophy patients
Becker Muscular Dystrophy (BMD) is caused by in-frame mutations in the DMD gene, leading to the production of internally truncated but partially functional dystrophin. Although cardiac involvement is a major contributor to disease burden in BMD, the cellular mechanisms driving cardiomyopathy remain incompletely understood. While emerging evidence suggests that iron imbalance may contribute to oxidative stress and mitochondrial dysfunction in muscular dystrophies, its role in BMD-associated cardiomyopathy has not been defined. Building on our previous findings of dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes from Duchenne muscular dystrophy (DMD), we investigated whether similar alterations are present in BMD using patient-specific and genome-corrected hiPSC-CM models. HiPSC lines derived from two BMD patients and their CRISPR/Cas9-corrected isogenic controls displayed normal karyotype, pluripotency, and efficient differentiation into cardiomyocytes (hiPSC-CMs). BMD hiPSC-CMs showed elevated ROS levels and decreased cytoplasmic and mitochondrial labile iron pools, accompanied by reduced expression of mitoNEET ( CISD1 ), a regulator of mitochondrial iron handling. We also detected changes in the expression of genes involved in iron storage ( FTH1 ), uptake ( TFRC ), and export ( SLC40A1 ), suggesting a dysregulation of iron trafficking. Importantly, correction of DMD mutation by CRISPR/Cas9 gene editing reversed the effects observed in BMD cardiomyocytes. These results extend our previous observations in DMD to BMD cardiomyocytes and suggest that full-length dystrophin is essential for maintaining cardiac iron homeostasis.
Open article ↗
2026-05-20 | Heart failure guideline-directed medical therapy in young adults with dystrophin-related cardiomyopathy: the HOPE-MD registry
BACKGROUND: Duchenne (DMD) and Becker (BMD) muscular dystrophies often progress to dilated cardiomyopathy and heart failure with reduced ejection fraction (HFrEF), a major cause of death in affected patients. Although guideline-directed medical therapy (GDMT) improves HFrEF outcomes, its real-world use in dystrophinopathies is poorly defined. We assessed GDMT utilization and optimization in the study population. METHODS: HOPE-MD is a European, multicentre, retrospective registry including adults with genetically confirmed DMD or BMD and left ventricular ejection fraction (LVEF) ≤40%. GDMT was defined as concurrent use of a renin-angiotensin system inhibitor (RASi), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter-2 inhibitor (SGLT2i). Doses were categorized as target (≥100%), intermediate (50-99%), or low (<50%). RESULTS: Among 274 patients (age, 28 years; LVEF, 35%; DMD, 80%), 44 (16%) received GDMT at baseline, with only one quarter at ≥50% of the target dose. Underutilization was greatest for MRAs (n=140, 51%) and SGLT2i (n=60, 22%), whereas RASi (n=246, 90%) and beta-blockers (n=235, 86%) were frequently prescribed. After 24 months (n=141), 40% received GDMT, and 22% received ≥50% of the target dose, primarily through MRA and SGLT2i initiation/uptitration. Contraindications accounted for only a small proportion of undertreatment. At a median follow-up of 2.2 (1.7-2.6) years, optimized GDMT was not associated with a statistically significant difference in the rates of death or HF hospitalization compared with low-dose or no GDMT (adjusted HR 0.70, 95% CI 0.28-1.74). CONCLUSIONS: GDMT use and dose escalation were suboptimal in European patients with DMD/BMD and HFrEF.
Open article ↗
2026-05-20 | Progressive Duchenne/Becker muscular dystrophy, preclinical stage, deletion of exons 45-55 of the DMD gene in the hemizygous state: a clinical case from practice
Background. Duchenne/Becker progressive muscular dystrophy is an X-linked recessive disease caused by mutations in the DMD gene encoding the dystrophin protein. Deletions of exons 45-55 often correspond to the principle of preserving the reading frame, being associated with the Duchenne/Becker muscular dystrophy phenotype. Objective. To present a clinical case of the presymptomatic diagnosis of progressive Duchenne/Becker muscular dystrophy in an early-age patient with deletion of exons 45-55 of the DMD gene, analyze diagnostic markers and justify a strategy for dynamic follow-up. Materials and methods. A retrospective analysis of medical documentation with clinical, laboratory and instrumental methods was performed. In order to form a theoretical base, data was searched and systematized from scientific electronic libraries (CyberLeninka, eLibrary, PubMed, Google Academy) on progressive Duchenne/Becker muscular dystrophy (preclinical phase) and deletion of exons 45-55 of the DMD gene. The review includes literature reviews, scientific publications, and the results of clinical trials on the topic. Conclusion. A clinical case of diagnosis of progressive Duchenne/Becker muscular dystrophy in a 1-year-old male patient with isolated hyperfermentemia (ALT – 120 U/l, AST – 107.1 U/L) and a significant increase in creatine phosphokinase (4817.1 U/L) is described. Conducted: biochemical examination (creatine phosphokinase, lactate dehydrogenase, creatine phosphokinase-MV), instrumental diagnostics, including electrocardiography, ultrasound examination of the heart and abdominal cavity), molecular genetic analysis. The molecular genetic analysis method verified the hemizygous deletion of exons 45-55 of the DMD gene. The diagnosis of progressive Duchenne/Becker muscular dystrophy was established at the preclinical stage, despite the absence of manifest neurological symptoms. The case demonstrates the critical role of determining of creatine phosphokinase as a screening marker and the need for an integrated approach for early diagnosis. The detection of in-frame deletion creates prerequisites for the potential use of exon-skipping therapy.
Open article ↗
