Abstract: Some embodiments of the methods and compositions provided herein relate to treating, inhibiting or ameliorating a skeletal muscular dystrophy with a polynucleotide encoding a SERCA2a polypeptide. In some embodiments, the muscular dystrophy comprises Duchenne muscular dystrophy (DMD) or Becker's muscular dystrophy (BMD). In some embodiments, the polynucleotide comprises a viral vector, such as an adeno-associated viral (AAV) vector. More embodiments include methods and compositions to screen for a therapeutic agent to treat, inhibit or ameliorate a skeletal muscular dystrophy in which the screen comprises an in vitro ventricular cardiac tissue model.