ETD

• Duchenne Muscular Dystrophy
• hiPSCs
• Lipidomics
• Metabolomics
• Organoids

Duchenne muscular dystrophy (DMD) is the most common neuromuscular dystrophy of the childhood. Caused by mutations in the DMD gene, which encodes dystrophin, a protein predominantly expressed in muscle tissue, it is inherited in a X linked recessive fashion. Dystrophin absence causes myofibres to be highly susceptible to contraction-induced injury, leading to progressive muscle weakness and degeneration. Beyond skeletal muscle, cardiac and respiratory functions are strongly affected. Indeed, cardiomyopathy represents the leading cause of premature mortality in patients affected with DMD, generally occurring between the third and fourth decade of life.
To date, no curative treatment is available, and the disease is managed primarily through symptomatic therapies. It must be noted that conventional animal and two-dimensional cellular models of the disease fail to recapitulate key aspects of DMD pathology. Consequently, In the last few years, organoids have emerged as a promising alternative to animal models in preclinical studies. In fact, organoids are three-dimensional, in vitro, self-organizing tissue systems that replicate many of the structural and functional features of native organs. Furthermore, since they can be derived from pluripotent cells, harbouring patients’ genotype, they represent highly relevant platforms to investigate disease mechanisms and evaluate novel therapeutic personalized strategies.
Given the central role of cardiac dysfunction in DMD, this study aimed to generate cardiac organoids from hiPSCs derived from patients affected by DMD as well as from healthy controls. A multi-omics approach, including lipidomics and metabolomics. was employed to comprehensively characterize this model and identify molecular differences between disease and control conditions.
As one of the few studies applying cardiac organoid to Duchenne muscular dystrophy, this work contributes to assess molecular alteration involved in this disease, to strengthen the use of organoids as valuable tools for disease modelling and to highlight the importance of omics approaches for the multidimensional molecular profiling of experimental models.