Pre-clinical study of 21 approved drugs in the mdx mouse
Pre-clinical study of 21 approved drugs in the mdx mouse
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DOI：
10.1016/j.nmd.2011.01.005
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发表时间：
2011-05-01
影响因子：
2.8
通讯作者：
Segalat, Laurent
中科院分区：
文献类型：
--
作者：
Carre-Pierrat, Maite;Lafoux, Aude;Segalat, Laurent
杜氏肌营养不良症是一种由于缺乏功能性肌营养不良蛋白而引起的遗传性疾病，目前仍没有得到充分的治疗。尽管人们对基因和细胞疗法寄予厚望，但活性小分子的鉴定仍然是新疗法的有效选择。我们研究了20种已批准的药物化合物对肌营养不良蛋白缺陷型mdx5Cv小鼠肌肉的影响。这些化合物是作为对无脊椎动物模型秀丽隐杆线虫的肌营养不良蛋白突变体的800种批准分子的先前筛选的结果而选择的。从出生后2周开始，通过母体喂养向小鼠给药，并在出生后3周混合在食物中。在6周和16周时评价药物对小鼠的影响。每种药物在两种浓度下进行测试。将泼尼松添加到分子列表中作为阳性对照。为了研究治疗效率，记录了30多个组织学、生化和功能参数。这项广泛的研究表明，三环类药物（丙咪嗪和阿米替林）对mdx小鼠的快速肌肉有益。它还强调了根据时间，肌肉和测定的反应的巨大可变性。(C)2011 Elsevier B.V.保留所有权利。
Duchenne muscular dystrophy, a genetic disease caused by the absence of functional dystrophin, remains without adequate treatment. Although great hopes are attached to gene and cell therapies, identification of active small molecules remains a valid option for new treatments.We have studied the effect of 20 approved pharmaceutical compounds on the muscles of dystrophin-deficient mdx5Cv mice. These compounds were selected as the result of a prior screen of 800 approved molecules on a dystrophin mutant of the invertebrate animal model Caenorhabditis elegans. Drugs were administered to the mice through maternal feeding since 2 weeks of life and mixed in their food after the 3rd week of life. The effects of the drugs on mice were evaluated both at 6 weeks and 16 weeks. Each drug was tested at two concentrations. Prednisone was added to the molecule list as a positive control. To investigate treatment efficiency, more than 30 histological, biochemical and functional parameters were recorded. This extensive study reveals that tricyclics (Imipramine and Amitriptyline) are beneficial to the fast muscles of mdx mice. It also highlights a great variability of responses according to time, muscles and assays. (C) 2011 Elsevier B.V. All rights reserved.