Building Duchenne in a dish: Engineered human Muscle Tissues (EMTs) for disease modelling and drug testing

Duchenne Muscular Dystrophy (DMD) is a severe and progressive X-linked neuromuscular disorder that is caused by mutations in the dystrophin gene, leading to the absence of a functional protein product. The lack of dystrophin results in myofibre degeneration, disruption of muscle integrity, loss of ambulation, and ultimately death due to cardiac or respiratory failure. Recent developments in DMD treatment have led to dystrophin replacement therapies, however secondary pathological alterations of the pathology still remain a big challenge. Therefore, there are no available treatments that are able to address the full complexity of DMD pathology. Despite the presence of well-established animal models for DMD, such as mdx mouse, no animal model fully recapitulates the complex phenotype typical of DMD patients. Nevertheless, different attempts at modelling this disease with human-derived cells have been able to reproduce specific features of DMD. Making use of the Mantarray platform (CuriBio), I have developed a 3D model of the skeletal muscle called Engineered Muscle Tissue (EMT), composed of patient-derived myoblasts and primary fibroblasts. Moreover, the Mantarray platform enables the incorporation of contractile parameters as primary functional readouts, therefore increasing the understanding of the model along with classical molecular and bioenergetic characterizations. The EMTs have been shown to recapitulate some typical aspects of DMD such as a disorganized myotubes distribution, delayed maturation of the muscle fibers and reduced expression of maturation markers.