glucocorticoid-treated mice are an inappropriate positive control for long-term preclinical studies in the mdx mouseglucocorticoid-treated老鼠是一个长期的临床前研究的积极控制不当mdx鼠标.pdfVIP

Glucocorticoid-Treated Mice Are an Inappropriate Positive Control for Long-Term Preclinical Studies in the mdx Mouse 1. 1. 1 3 Arpana Sali , Alfredo D. Guerron , Heather Gordish-Dressman , Christopher F. Spurney , Micaela Iantorno1, Eric P. Hoffman1,2, Kanneboyina Nagaraju1,2* 1 Research Center for Genetic Medicine, Children’s National Medical Center, Washington DC, United States of America, 2 Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, United States of America, 3 Division of Cardiology, Children’s National Medical Center, Washington DC, United States of America Abstract Background: Dmdmdx (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations. Methods and Findings: We performed nine pre-clinical efficacy trials (treated N = 129, untreated N = 106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of