• V Marrocco, P Fiore, A Benedetti, S Pisu, E Rizzuto, A Musarò, L Madaro, B Lozanoska-Ochser, and M Bouché.
• Dept. of Anatomy, Histology, Forensic Medicine and Orthopedics, Unit of Histology and Med. Embryology, CE-BEMM and Interuniversity Institute of Myology, Sapienza University of Rome, 00161 Rome, Italy.
• EBioMedicine. 2017 Feb 1; 16: 150-161.

AbstractInflammation plays a considerable role in the progression of Duchenne Muscular Dystrophy (DMD), a severe muscle disease caused by a mutation in the dystrophin gene. We previously showed that genetic ablation of Protein Kinase C θ (PKCθ) in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20). We show that C20 treatment led to a significant reduction in muscle damage associated with reduced immune cells infiltration, reduced inflammatory pathways activation, and maintained muscle regeneration. Importantly, C20 treatment is efficient in recovering muscle performance in mdx mice, by preserving muscle integrity. Together, these results provide proof of principle that pharmacological inhibition of PKCθ in DMD can be considered an attractive strategy to modulate immune response and prevent the progression of the disease.Copyright © 2017 3-V Biosciences. Published by Elsevier B.V. All rights reserved.

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