Pharmacological treatment of Duchenne muscular dystrophy (DMD) with histone deacetylase inhibitors (HDACi) is currently being tested in clinical trials; however, pre‐clinical studies indicated that the beneficial effects of HDACi are restricted to early stages of disease. We show that FAPs from late‐stage mdx mice exhibit aberrant HDAC activity and genome‐wide alterations of histone acetylation that are not fully reversed by HDACi. In particular, combinatorial H3K27 and/or H3K9/14 hypo‐acetylation at promoters of genes required for cell cycle activation and progression, as well as glycolysis, are associated with their downregulation in late‐stage mdx FAPs. These alterations could not be reversed by HDACi, due to a general resistance to HDACi‐induced H3K9/14 hyperacetylation. Conversely, H3K9/14 hyper‐acetylation at promoters of Senescence Associated Secretory Phenotype (SASP) genes is associated with their upregulation in late‐stage mdx FAPs; however, HDACi could reduce promoter acetylation and blunt SASP gene activation. These data reveal that during DMD progression FAPs develop disease‐associated features reminiscent of cellular senescence, through epigenetically distinct and pharmacologically dissociable events. They also indicate that HDACi might retain anti‐fibrotic effects at late stages of DMD.

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration due to mutations in the dystrophin gene. Despite major advancements in understanding its pathophysiology, there is still no curative treatment. This review provides an up-to-date overview of current and emerging therapeutic approaches—including antisense oligonucleotides, gene therapy, gene editing, corticosteroids, and histone deacetylases(HDAC) inhibitors—aimed at restoring dystrophin expression or mitigating disease progression. Special emphasis is placed on the importance of early diagnosis, the utility of genetic screening, and the innovations in pre-and post-natal testing. As the field advances toward personalized medicine, the integration of precision therapies with cutting-edge diagnostic technologies promises to improve both prognosis and quality of life for individuals with DMD.

Recent studies have revealed the contribution of fibro-adipogenic progenitors (FAPs) to the pathogenesis and progression of Duchenne Muscular Dystrophy (DMD). While FAPs direct compensatory regeneration at early stages of disease, as the disease progresses they contribute to the progressive replacement of contractile myofibers with fibrotic scars and fatty infiltration. Using the mouse model of DMD – the mdx mice - we have recently reported that FAPs mediate the ability of HDAC inhibitors (HDACi) to promote muscle regeneration and prevent fibro-adipogenic degeneration at early stages of disease. This effect is mediated by the induction of myomiRs that, in turn, target the SWI/SNF components BAF60A and B, thereby favoring the formation of BAF60C-based SWI/SNF complex, which directs the switch from the fibro-adipogenic to the myogenic lineage. Here we show direct evidence of induction of miR-206 and BAF60C, and reduction of BAF60A, in FAPs isolated from mdx muscles exposed to the HDACi Trichostatin A (TSA)....

Here, we present a one-pot procedure for the preparation of hyaluronic acid (HA) sulfonated hydrogels in aqueous alkaline medium. The HA hydrogels were crosslinked using 1,4-butanedioldiglycidyl ether (BDDE) alone, or together with N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (Bes), as a safe sulfonating agent. Conditions for the simultaneous reaction of HA with BDDE and Bes were optimized and the resulting hydrogels were characterized under different reaction times (24, 72, and 96 h). The incorporation of sulfonic groups into the HA network was proven by elemental analysis and FTIR spectroscopy and its effect on water uptake was evaluated. Compared with the non-sulfonated sample, sulfonated gels showed improved mechanical properties, with their compressive modulus increased from 15 to 70 kPa, higher stability towards hyaluronidase, and better biocompatibility to 10T1/2 fibroblasts, especially after the absorption of collagen. As main advantages, the procedure described represents an easy and reproducible methodology for the fabrication of sulfonated hydrogels, which does not require toxic chemicals and/or solvents.

Duchenne Muscular Dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration due to mutations in the dystrophin gene. Despite major advancements in understanding its pathophysiology, there is still no curative treatment. This review provides an up-to-date overview of current and emerging therapeutic approaches— including antisense oligonucleotides, gene therapy, gene editing, corticosteroids, and HDAC inhibitors— aimed at restoring dystrophin expression or mitigating disease progression. Special emphasis is placed on the importance of early diagnosis, the utility of genetic screening and the innovations in pre- and post- natal testing. As the field advances toward personalized medicine, the integration of precision therapies with cutting-edge diagnostic technologies promises to improve both prognosis and quality of life for individuals with DMD.