Advanced in vitro modelling of neuromuscular diseases and gene therapies

The Tedesco laboratory (www.tedescolab.org) harness the regenerative potential of muscle stem cells to create innovative models to study and develop therapies for incurable neuromuscular disorders. Their work pioneered engineering and pre-clinical translation of artificial chromosomes as gene therapy vectors (Tedesco et al., Sci Transl Med 2011; Benedetti et al., EMBO Mol Med 2018), as well as generation, differentiation, genetic correction and pre-clinical testing of human induced pluripotent stem cells (iPSCs) from patients with muscular dystrophy (Tedesco et al., Sci Transl Med 2012; Maffioletti et al., Nat Protoc 2015). More recently, they developed the first 3D human muscle model containing up to 4 distinct isogenic cell lineages capable to model disease-associated phenotypes with high resolution and fidelity, and to support testing of advanced therapies such as gene therapy vectors and myogenic cell transplantation (e.g. Maffioletti et al., Cell Reports 2018; Choi et al., EMBO Mol Med 2022; Pinton et al., Nat Protoc 2023). During his talk Prof. Tedesco will present recent advances in modelling severe congenital muscle disorders using their platforms, as well as efforts towards modelling neuromuscular genetic therapies using engineered muscle constructs.