Novel Therapeutic Approaches for Skeletal Muscle Dystrophies

Muscular dystrophies (MDs) are inherited diseases that affect skeletal and cardiac muscle tissues. Cases range from mild to very severe, resulting in respiratory or cardiac failures. No cures are available for MDs and corticosteroid treatments, mainly deflazacort and prednisolone, only help to control the inflammatory process and slightly delay the progression of the disease. This is due to the beneficial effect on pulmonary function and scoliosis. Walkers and wheelchairs are used to strengthen patients’ independence and walking ability. When respiratory and/or cardiac muscles become weak, mechanical ventilation is mandatory. In addition, hypertension, cataracts, excessive weight gain and vertebral fracture are often serious side effects of deflazacort and prednisolone treatments. This chapter deals with the advanced therapies used to treat muscle degenerations, ranging from pharmacological to gene and/or cell treatments. We review previous trials that use cell delivery protocols in mice and patients. Here, donor satellite cells and myogenic progenitors are isolated from the bone marrow. We then proceed to describe the recently identified stem/progenitor cells in relation to their ability to exist within a dystrophic muscle and to differentiate into skeletal muscle cells. In this perspective, different known features of various stem cells are compared including mesoangioblasts and mesoderm-derived stem cells, which are associated with the pericyte compartment. This chapter also provides an outline of the latest techniques used for the isolation/ generation and characterization of pluripotent and adult stem cells. We focus on their myogenic differentiation potential and the different strategies used for genetic manipula‐ tion including TALEN and CRISPR genome editing. We also explore the use of microRNAs as biological markers or as possible therapeutic targets to improve myogenic commitment of pluripotent and adult stem cells. Finally, based on the rapid advance in stem cell technology, we discuss a prediction of clinical translation for novel cell therapy protocols.