Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Muscle Nerve. 2010 Nov;42(5):722-30. doi: 10.1002/mus.21743.
Modulation of transforming growth factor-β (TGF-β) signaling to promote muscle growth holds tremendous promise for the muscular dystrophies and other disorders involving the loss of functional muscle mass. Previous studies have focused on the TGF-β family member myostatin and demonstrated that inhibition of myostatin leads to muscle growth in normal and dystrophic mice. We describe a unique method of systemic inhibition of activin IIB receptor signaling via adeno-associated virus (AAV)-mediated gene transfer of a soluble form of the extracellular domain of the activin IIB receptor to the liver. Treatment of mdx mice with activin IIB receptor blockade led to increased skeletal muscle mass, increased force production in the extensor digitorum longus (EDL), and reduced serum creatine kinase. No effect on heart mass or function was observed. Our results indicate that activin IIB receptor blockade represents a novel and effective therapeutic strategy for the muscular dystrophies.
转化生长因子-β（TGF-β）信号的调节有望治疗肌肉萎缩症和其他涉及功能性肌肉减少的疾病。先前的研究集中在 TGF-β 家族成员肌肉生长抑制素上，并证明抑制肌肉生长抑制素可导致正常和营养不良小鼠的肌肉生长。我们描述了一种通过腺相关病毒（AAV）介导的将激活素 IIB 受体胞外结构域的可溶性形式转移到肝脏中来系统抑制激活素 IIB 受体信号的独特方法。用激活素 IIB 受体阻断剂治疗 mdx 小鼠可增加骨骼肌质量，增加伸趾长肌（EDL）的力产生，并降低血清肌酸激酶。未观察到对心脏质量或功能的影响。我们的结果表明，激活素 IIB 受体阻断剂代表了肌肉萎缩症的一种新的有效治疗策略。
