Mouse Anti Human Dystrophin Hybridoma [NBOESB25(3G3)]

Introduction: Duchenne muscular dystrophy (DMD) is the result of X-chromosome-linked mutations to the dystrophin protein gene that prevent the normal development and repair of muscles leading to muscle deterioration. The condition affects nearly 1 in 3,500 males worldwide. Current therapeutics have not been sufficient in providing a cure or resulting in a significant extension in life expectancy, but many therapeutic options are currently under investigation. Areas covered: This article provides an overview of the current and emerging therapies for DMD giving particular focus to synthetic therapeutic options. The authors further provide their expert opinion. Expert opinion: Many discrepancies in primary outcomes of trials have led to questions of efficacy for medications, as well as difficulty in securing FDA approval. A standardization of primary outcome strategies, as well as better access to investigational medications, may alleviate some of the controversy and pressures that exist on medication approvals. Many trials have identified cohorts who responded more favorably to medications, despite a lack of significance in the overall intent-to-treat populations. This indicates that more medication screening and personalized treatment with patient-specific targeting might deliver more clinically significant results.

Satellite cells (SCs) are muscle stem cells that remain quiescent during homeostasis and are activated in response to acute muscle damage or in chronic degenerative conditions such as Duchenne Muscular Dystrophy. The activity of SCs is supported by specialized cells which either reside in the muscle or are recruited in regenerating skeletal muscles, such as for instance macrophages (M Phi s). By using a dystrophic mouse model of transient M Phi depletion, we describe a shift in identity of muscle stem cells dependent on the crosstalk between M Phi s and SCs. Indeed M Phi depletion determines adipogenic conversion of SCs and exhaustion of the SC pool leading to an exacerbated dystrophic phenotype. The reported data could also provide new insights into therapeutic approaches targeting inflammation in dystrophic muscles. Author summary Muscular dystrophies are a heterogenous group of genetic disorders characterized by muscle wasting, leading to loss of mobility and eventually to death due to respiratory or cardiac failure. Duchenne Muscular Dystrophy (DMD) is one of the most severe dystrophies and is caused by the loss of functional dystrophin protein owing to genetic mutations, consequently, the sarcolemma becomes fragile and susceptible to muscle damage induced by contraction. Satellite cells (SCs) are skeletal muscle stem cells that mediate the repair process leading to muscle regeneration. Dystrophic muscles undergo continuous cycles of degeneration and regeneration eventually culminating in myofiber loss and deposition of fibrous and fatty connective tissue. Inflammation is always associated with the muscle regeneration process. Among different types of inflammatory cells, mainly macrophages (M Phi s) are present in regenerating skeletal muscles and are involved in the regenerative process both after an acute injury and during pathological conditions such as DMD. We focused on the cross-talk between M Phi s and SCs in a mouse model of DMD and highlighted a role of M Phi s in preserving the SC identity.