Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice.
Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice.
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DOI：
10.1089/10430340260185085
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发表时间：
2002-08
影响因子：
4.2
通讯作者：
J. Watchko;T. O'Day;Bing Wang;Liqiao Zhou;Ying Tang;Juan Li;Xiao Xiao-Xiao
中科院分区：
文献类型：
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作者：
J. Watchko;T. O'Day;Bing Wang;Liqiao Zhou;Ying Tang;Juan Li;Xiao Xiao-Xiao
杜氏肌营养不良症（DMD）是最常见的致残性和致命性遗传性肌肉疾病，每3500名男性中就有1名患有DMD。DMD患者经历进行性肌肉变性和虚弱，并在二十出头时死于呼吸或心力衰竭。目前尚无治疗DMD的方法。肌营养不良蛋白基因的突变导致横纹肌中功能性肌营养不良蛋白的缺乏，其诱导肌细胞膜的不稳定性，导致收缩后的持续性肌肉损伤。我们以前已经创建了新的minidystrophin基因，并证明腺相关病毒（AAV）介导的肌内递送的minigenes有效地改善mdx营养不良的组织病理学，并导致正常的细胞膜完整性超过1年。在本文中，我们调查是否AAV-minidystrophin也可以改善mdx肌肉收缩功能。将具有已建立的肌营养不良症的两个月大的成年雄性mdx小鼠在一条腿的胫骨前肌（TA）肌肉中给予AAV-小型肌萎缩蛋白载体的单次剂量注射，将未处理的对侧腿用作对照。经处理的TA肌肉显示出（1）等长力产生的显著增加和（2）对延长激活诱导的肌肉力量递减的抵抗力的显著增加。我们的结论是，AAV-minidystrophin基因治疗是有效的，在改善mdx肌肉收缩功能。
Duchenne muscular dystrophy (DMD) is the most common disabling and lethal genetic muscle disorder, afflicting 1 of every 3500 males. Patients with DMD experience progressive muscle degeneration and weakness and succumb to respiratory or cardiac failure by their early twenties. No treatment is currently available for DMD. Mutations in the dystrophin gene result in lack of a functional dystrophin protein in striated muscle, which induces instability in the muscle cell membrane leading to persistent muscle injury after contraction. We have previously created novel minidystrophin genes and demonstrated that adeno-associated virus (AAV)-mediated intramuscular delivery of the minigenes effectively ameliorated mdx dystrophic histopathology and led to normal cell membrane integrity for more than 1 year. In this paper, we investigated whether AAV-minidystrophin could also improve mdx muscle contractile function. Two-month-old adult male mdx mice, with established muscular dystrophy, were given a single-dose injection of an AAV-minidystrophin vector in the tibialis anterior (TA) muscle of one leg, with the untreated contralateral leg used as a control. The treated TA muscle showed both (1) a significant increase in isometric force generation and (2) a significant increase in resistance to lengthening activation-induced muscle force decrements. We conclude that AAV-minidystrophin gene treatment is effective in improving mdx muscle contractile function.