Muscular Dystrophies: Current Therapeutic Advances to Improve and Restore Muscle Homeostasis

Skeletal muscle is a heterogeneous tissue representing between 30% - 38% of the human body mass and has important functions in the organism, such as maintaining posture, locomotor impulse, or pulmonary ventilation. The genesis of skeletal muscle during embryonic development is a process controlled by an elaborate regulatory network that transforms myogenic precursor cells into functional muscle fibers through a finely tuned differentiation program. Adult myogenesis resembles many of the embryonic morphogenetic episodes, being fundamental for muscle regeneration and homeostasis. Muscular dystrophies (MDs) are the most important group among primary muscular disorders in terms of the number of people affected and economic impact generated in public health systems. These pathologies are inherited myogenic disorders characterized by progressive muscle wasting and weakness of variable distribution and severity, where muscle maintenance is compromised.

Experimental strategies aimed to improve the muscle homeostasis have emerged as a therapeutic goal to explore. The homeostasis of muscle mass depends on a delicate balance between regeneration and degradation pathways. It has been emphasized that, in MDs, progressive muscle wasting and weakness is often associated with the exhaustion of muscle regeneration potential. In this sense, the progressive loss of muscle mass has been attributed, at least partly, to the inability of muscle stem cells to efficiently regenerate tissue loss and/or to overactivation of protein-degradation pathways as the result of the disease. To date, several approaches have been implemented to enhance dystrophic muscle regeneration capabilities within these MDs, either by improving muscle stem cell regeneration capabilities or by blocking the overactivation of protein-degradation pathways in myocytes. Unfortunately, complete muscle restoration has not yet been accomplished in patients.

The aim of this research topic is to explore the current approaches implemented to enhance muscle regeneration in MDs by boosting muscle biogenesis or inhibiting its degradation. We welcome original research and review articles that cover the following themes:

- New approaches related to cell and gene therapies to promote muscle stem cell differentiation, or reduce activity of muscle degradation pathways.

- Therapeutic strategies based on oligonucleotides implemented to promote muscle stem cell differentiation, or reduce activity of muscle degradation pathways.

- Misregulation of cross-talk between muscle stem cells and the rest of muscular cells within MD context, and how it contributes to enhance fibrosis and adipogenesis in these pathologies.

- Discussions on the involvement of pathways that have recently been described as key factors in muscle mass maintenance such as autophagy, apoptosis and ubiquitin-proteasome system.

- Drug development within the MD field.

Keywords: Muscular dystrophies, muscle stem cell, regeneration, autophagy, apoptosis, ubiquitin-proteasome system

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