Cannabidiol-induced Heme oxygenase-1 contributes to modulate the phenotype of hiPSC-derived cardiac fibroblasts from patients with Duchenne muscular dystrophy

Niclosamide reprograms macrophages and improves muscle integrity in Duchenne muscular dystrophy models.

Duchenne Muscular Dystrophy (DMD) is a severe X-linked disorder characterized by progressive degeneration of skeletal and cardiac muscles caused by mutations in the DMD gene encoding dystrophin, a protein essential for cytoskeletal integrity and muscle function. A truncated dystrophin leads to increased muscle susceptibility to contraction-induced damage, driving chronic inflammation and fibrosis. Although corticosteroids remain the standard of care, novel therapeutic strategies are urgently needed. Niclosamide, a long-established anthelmintic drug, has recently been repurposed in inflammatory and fibrotic conditions, including neuromuscular diseases. We investigated the effects of niclosamide in vitro using primary macrophages from mdx mice, human DMD myoblasts, and murine C2C12 myoblast cultures, and in vivo in a proof-of-concept study in mdx mice. In primary mdx macrophages, niclosamide reduced inflammation and reactive oxygen species production, while promoting an anti-inflammatory/pro-regenerative phenotype. In parallel, niclosamide enhanced the differentiation of human DMD myoblasts, and conditioned medium from niclosamide-treated macrophages significantly improved C2C12 myoblast differentiation. In treated mdx mice, niclosamide improved muscle resistance and reduced muscle damage, as indicated by decreased plasma creatine kinase levels and lower immunoglobulin infiltration. These effects were accompanied by modulation of key markers involved in muscle proliferation and differentiation, supporting a beneficial role of niclosamide in promoting muscle repair in dystrophic muscle. Overall, these findings indicate that niclosamide promotes an anti-inflammatory and pro-regenerative environment, enhancing myoblast differentiation and limiting muscle degeneration, supporting its potential role as a promising therapeutic candidate for Duchenne muscular dystrophy.

Alpha-ketoglutarate ameliorates diabetes-associated skeletal muscle fibrosis by restoring TET2-dependent epigenetic remodeling in CD90 positive fibro-adipogenic progenitors.

Dysregulation of α-KG and L-2HG drives diabetic muscle fibrosis by disrupting TET2-dependent DNA hydroxymethylation and FAP division symmetry, supporting a TET2-dependent mechanism underlying the epigenetic effects of α-KG.

ATP6AP2 dysregulation as a central hub in DMD pathogenesis: An integrated multi-omics and therapeutic study.

It is demonstrated that TMZ mitigates dystrophic pathology by targeting the ATP6AP2 signaling axis and dampening macrophage-mediated inflammatory responses, highlighting its potential as a novel immunopharmacological therapeutic strategy for DMD.

Characterizing the Roles of Dysferlin Deficiency in Function, Polarization, and Secretome of Human iPSC-Derived Macrophages 2251399

Dysferlin loss in iMPs results in cell-autonomously altered transcriptome, secretome, and endocytic function, which may contribute to LGMDR2 muscle pathology and disease progression.

Lanifibranor (IVA-337) - a pan-PPAR agonist suppresses TGF-β1-induced cardiac fibrosis and rescues cardiomyocyte function

YAP1-Driven Pathogenic Fibro-Adipogenic Progenitors Secrete IL-6 and FGF21 to Mediate Muscle-Bone Crosstalk and Promote Bone Loss.

It is shown that dysregulated endocrine function of skeletal muscle promotes bone loss through YAP1-driven pathogenic FAPs secreting IL-6 and FGF21, identifying FAP-derived IL-6 and FGF21 as key mediators of muscle-bone crosstalk and establishing the YAP-FAP-myokine axis as a therapeutic target for preventing bone loss in sarcopenia and osteoporosis.