PURPOSE: Histone Deacetylase Inhibitors (DI) ameliorates dystrophic muscle regeneration restoring muscular strength in the mdx mouse model of Duchenne muscular dystrophy (DMD). The further development of these compounds as drugs for DMD treatment is currently hampered by the lack of knowledge about DIs effect in large dystrophic animal models and that of suitable biomarkers to monitor their efficacy. EXPERIMENTAL DESIGN: In this study we applied proteomic analysis to identify differentially expressed proteins present in plasma samples from mdx mice treated with the Suberoylanilide hydroxamic acid (SAHA) and relative normal controls (WT). RESULTS: Several differentially expressed proteins were identified between untreated wild type and mdx mice. Among these, fibrinogen, epidermal growth factor 2 receptor, major urinary protein and glutathione peroxidase 3 (GPX3) were constitutively up-regulated in mdx, while complement C3, complement C6, gelsolin, leukaemia inhibitory factor receptor (LIFr), and alpha 2 macroglobulin were down-regulated compared to WT mice. SAHA determined the normalization of LIFr and GPX3 protein level while apoliprotein E was de novo up-regulated in comparison to vehicle-treated mdx mice. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these data unravel potential serological disease biomarkers of mdx that could be useful to monitor muscular dystrophy response to DI treatment.
PURPOSE: Histone Deacetylase Inhibitors (DI) ameliorates dystrophic muscle regeneration restoring muscular strength in the mdx mouse model of Duchenne muscular dystrophy (DMD). The further development of these compounds as drugs for DMD treatment is currently hampered by the lack of knowledge about DIs effect in large dystrophic animal models and that of suitable biomarkers to monitor their efficacy. EXPERIMENTAL DESIGN: In this study we applied proteomic analysis to identify differentially expressed proteins present in plasma samples from mdx mice treated with the Suberoylanilide hydroxamic acid (SAHA) and relative normal controls (WT). RESULTS: Several differentially expressed proteins were identified between untreated wild type and mdx mice. Among these, fibrinogen, epidermal growth factor 2 receptor, major urinary protein and glutathione peroxidase 3 (GPX3) were constitutively up-regulated in mdx, while complement C3, complement C6, gelsolin, leukaemia inhibitory factor receptor (LIFr), and alpha 2 macroglobulin were down-regulated compared to WT mice. SAHA determined the normalization of LIFr and GPX3 protein level while apoliprotein E was de novo up-regulated in comparison to vehicle-treated mdx mice. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these data unravel potential serological disease biomarkers of mdx that could be useful to monitor muscular dystrophy response to DI treatment.
Authors: Steven Carberry; Heinrich Brinkmeier; Yaxin Zhang; Claudia K Winkler; Kay Ohlendieck Journal: Int J Mol Med Date: 2013-07-03 Impact factor: 4.101
Authors: Burcu Ayoglu; Amina Chaouch; Hanns Lochmüller; Luisa Politano; Enrico Bertini; Pietro Spitali; Monika Hiller; Eric H Niks; Francesca Gualandi; Fredrik Pontén; Kate Bushby; Annemieke Aartsma-Rus; Elena Schwartz; Yannick Le Priol; Volker Straub; Mathias Uhlén; Sebahattin Cirak; Peter A C 't Hoen; Francesco Muntoni; Alessandra Ferlini; Jochen M Schwenk; Peter Nilsson; Cristina Al-Khalili Szigyarto Journal: EMBO Mol Med Date: 2014-07 Impact factor: 12.137
Authors: Anna M L Coenen-Stass; Graham McClorey; Raquel Manzano; Corinne A Betts; Alison Blain; Amer F Saleh; Michael J Gait; Hanns Lochmüller; Matthew J A Wood; Thomas C Roberts Journal: Sci Rep Date: 2015-11-23 Impact factor: 4.379