Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.
Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.
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抑制肌肉生长抑制素并不能改善严重脊髓性肌萎缩症小鼠的疾病特征。
DOI：
10.1093/hmg/ddp253
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发表时间：
2009
影响因子：
3.5
通讯作者：
Wagner,KathrynR
中科院分区：
文献类型：
--
作者：
Sumner,CharlotteJ;Wee,ClaribelD;Warsing,LeighC;Choe,DongW;Ng,AndrewS;Lutz,Cathleen;Wagner,KathrynR
目前尚无针对遗传性运动神经元疾病脊髓性肌萎缩症（SMA）的治疗方法。严重的 SMA 会导致运动神经元损失减少、肌纤维发育受损、严重肌无力和早期死亡。肌肉生长抑制素是一种转化生长因子-β 家族成员，可抑制肌肉生长。在原发性肌肉疾病和运动神经元疾病、肌萎缩侧索硬化症小鼠模型中，肌生长抑制素信号传导的丧失或阻断会增加肌肉质量并提高肌肉力量。在这项研究中，我们通过两种独立的策略评估了阻断严重 SMA 小鼠 (hSMN2/delta7SMN/mSmn−/−) 中肌生长抑制素信号传导的效果：(i) 肌生长抑制素抑制剂卵泡抑素的转基因过度表达和 (ii) 出生后施用可溶性激活素受体 IIB (ActRIIB-Fc)。过度表达卵泡抑素的 SMA 小鼠肌肉质量几乎没有增加，运动功能或生存率也没有改善。与媒介物处理的小鼠相比，ActRIIB-Fc 处理的 SMA 小鼠运动功能改善甚微，并且生存期没有延长。这些结果共同表明，对于严重形式的 SMA，抑制肌生长抑制素可能不是一种有前途的治疗策略。
There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn−/−) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.