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Reduction in pathological features of DMD from use of utrophin up-regulation.

Reduction in secondary pathological features. (A) Data demonstrates the reduction in overall skeletal muscle inflammation and fibrosis from mdx treated with SMT C1100 compared to vehicle only. SMT C1100 (50 mg/kg) or vehicle was delivered daily by oral gavage to groups of six mdx mice aged around 17 d for a total of 28 days. The TA, EDL, soleus, and diaphragm were removed and five sections from each muscle were stained and analysed blind by a board-certified veterinary pathologist for evidence of inflammation and fibrosis using a standard pathology scoring method described in the methods section. Scoring (0–3) was made for each section from each muscle then averaged for all muscles to give an overall assessment of improvement in the pathological effects of dystrophin deficiency; (B) Qualitative assessment of EDL muscle from SMT C1100-dosed mdx scored as 1=mild - occasional mononuclear inflammatory cells in the inter-bundle connective tissue with focal aggregations of mononuclear inflammatory cells. The arrows mark foci of inflammation. Qualitative assessment of EDL dosed with vehicle and scored as 2=moderate - multiple foci of mononuclear inflammatory cell infiltration in the inter-bundle connective tissue; occasional mononuclear inflammatory cells between individual muscle fibres.

PLoS One. 2011 May 6;6(5):e19189. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A, Wilson FX, Wren SP, De Luca A, Davies KE. Source Summit plc, Abingdon, United Kingdom. Jon.Tinsley@summitplc.com

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