Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about potential drug effectiveness
Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about potential drug effectiveness
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DOI：
10.1016/s0960-8966(02)00100-1
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发表时间：
2002-10-01
影响因子：
2.8
通讯作者：
Camerino, DC
中科院分区：
文献类型：
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作者：
De Luca, A;Pierno, S;Camerino, DC
Duchenne营养不良的对症药物治疗效果差，糖皮质激素是唯一显示出一定疗效的化合物，尽管它们的使用受到严重副作用的限制。对禁用药物的临床前试验需要可靠的人类疾病动物模型来预测药物对患者的有效性。运动的mdx小鼠在体内形成典型的肌肉无力模式，这已经被用作评价药物有效性的指标。我们已经证明，宏观电导氯离子，发生在mdx小鼠肌肉的变性再生事件的指数，是专门受损的慢性运动方案，是敏感的体内给药药物的作用，通过刺激再生（胰岛素样生长因子-1和类固醇）或通过抵消钙诱导的变性或炎症（牛磺酸和类固醇）。对氯离子电导的监测还允许评价假阳性化合物，其对小鼠体内力量有效但在肌肉水平无效，以及与其他细胞参数的功能相关性。(C)2002 Elsevier Science B. V.保留所有权利。
The symptomatic pharmacological therapy of Duchenne dystrophy is poor, glucocorticoids being the sole compounds showing a certain efficacy, although their use is restricted by serious side effects. Pre-clinical trials of prompt-to-use drugs need reliable animal models of the human disease to predict drug effectiveness in patients. The exercised mdx mouse develops a typical pattern of muscle weakness in vivo, which has already been used as an index on which to evaluate drug effectiveness. We have demonstrated that the macroscopic conductance to chloride ion, an index of degeneration-regeneration events occurring in mdx mouse muscles, is specifically impaired by a chronic exercise protocol and is sensitive to the action of in vivo administered drugs acting either by stimulating regeneration (insulin-like growth factor-1 and steroids) or by counteracting calcium-induced degeneration or inflammation (Taurine and steroids). The monitoring of conductance to chloride ion also allows the evaluation of false positive compounds, effective on mouse strength in vivo but not at muscle level, and the functional correlation with other cellular parameters. (C) 2002 Elsevier Science B.V. All rights reserved.