1,721,256 research outputs found
Extracellular vesicles and Duchenne muscular dystrophy pathology: Modulators of disease progression
Full text linkDuchenne muscular dystrophy (DMD) is a devastating disorder and is considered to be one of the worst forms of inherited muscular dystrophies. DMD occurs as a result of mutations in the dystrophin gene, leading to progressive muscle fiber degradation and weakness. Although DMD pathology has been studied for many years, there are aspects of disease pathogenesis and progression that have not been thoroughly explored yet. The underlying issue with this is that the development of further effective therapies becomes stalled. It is becoming more evident that extracellular vesicles (EVs) may contribute to DMD pathology. EVs are vesicles secreted by cells that exert a multitude of effects via their lipid, protein, and RNA cargo. EV cargo (especially microRNAs) is also said to be a good biomarker for identifying the status of specific pathological processes that occur in dystrophic muscle, such as fibrosis, degeneration, inflammation, adipogenic degeneration, and dilated cardiomyopathy. On the other hand, EVs are becoming more prominent vehicles for custom-engineered cargos. In this review, we will discuss the possible contribution of EVs to DMD pathology, their potential use as biomarkers, and the therapeutic efficacy of both, EV secretion inhibition and custom-engineered cargo delivery.sponsorship: The work done in the authors' laboratory is supported by Small Research Infrastructure KU Leuven-BioAssemblyBot 400 (KA/20/088), Research Foundation Flanders (FWO) (#G066821N), INTERREG-Euregio Meuse-Rhine (GYM, Generate your muscle 2020-EMR116), and the Italian Ministry of Health, Ricerca Finalizzata (RF-2019-12369703). MS is a recipient of the Hercules Foundation grant (AKUL/19/34) for the financing provided to purchase the high throughput calcium imaging system. (Small Research Infrastructure KU Leuven-BioAssemblyBot 400|KA/20/088, Research Foundation Flanders (FWO)|G066821N, INTERREG-Euregio Meuse-Rhine, Italian Ministry of Health, Ricerca Finalizzata|RF-2019-12369703, Hercules Foundation|AKUL/19/34)status: Publishe
The mesmiRizing complexity of microRNAs for striated muscle tissue engineering
Full text linkAbstractmicroRNAs (miRs) are small non-protein-coding RNAs, able to post-transcriptionally regulate many genes and exert pleiotropic effects. Alteration of miR levels in tissues and in the circulation has been associated with various pathological and regenerative conditions. In this regard, tissue engineering of cardiac and skeletal muscles is a fascinating context for harnessing the complexity of miR-based circuitries and signals. In this review, we will focus on miR-driven regulation of cardiac and skeletal myogenic routes in homeostatic and challenging states. Furthermore, we will survey the intriguing perspective of exosomal and circulating miRs as novel paracrine players, potentially useful for current and future approaches of regenerative medicine for the striated muscles
New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials.
Full text linkMuscular dystrophies primarily affect skeletal muscle. Mutations in a large number of genes, mainly encoding cytoskeletal proteins, cause different forms of dystrophy that compromise patient mobility and quality of life, and in the most severe cases lead to complete paralysis and premature death. Although muscular dystrophies still lack an effective therapy, several novel strategies are entering or are ready to enter clinical trials. Here we review the main experimental strategies, namely drug, gene and cell therapies, outlining their goals and limitations. We also provide an update of ongoing or planned clinical trials based on these strategies.sponsorship: Hosp San Raffaele, Stem Cell Res Inst, I-20132 Milan, Italy; Univ Pavia, Dept Expt Med, Human Anat Sect, I-27100 Pavia, Italy; Catholic Univ Louvain, Stem Cell Res Inst, B-3000 Louvain, Belgiumstatus: Publishe
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