Follistatin gene delivery enhances muscle growth and strength in nonhuman primates.
Follistatin gene delivery enhances muscle growth and strength in nonhuman primates.
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DOI：
10.1126/scitranslmed.3000112
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发表时间：
2009-11-11
影响因子：
17.1
通讯作者：
Kaspar BK
中科院分区：
文献类型：
--
作者：
Kota J;Handy CR;Haidet AM;Montgomery CL;Eagle A;Rodino-Klapac LR;Tucker D;Shilling CJ;Therlfall WR;Walker CM;Weisbrode SE;Janssen PM;Clark KR;Sahenk Z;Mendell JR;Kaspar BK
肌肉抑制素是一种由肌肉细胞产生的血液传播的肌肉生长负调节因子，其拮抗剂在啮齿动物研究中显示出增强肌肉质量和力量的巨大前景，并可能成为治疗人类肌肉疾病的潜在药物。其中最有效的药物之一，卵泡抑素，在小鼠身上既安全又有效，但类似的试验还没有在非人类灵长类动物身上进行。为了评估临床翻译的这一重要标准，我们测试了一种可替代剪接形式的人卵泡抑素，它影响骨骼肌，但对非肌肉细胞只有最小的影响。当注射入食蟹猴的股四头肌时，从腺相关病毒血清1型载体AAV1-FS344表达的卵泡抑素亚型诱导肌肉大小和力量显著和持久的增加。转基因的长期表达没有对关键器官的形态或功能产生任何异常变化，表明肌肉注射AAV1载体的基因传递是安全的。我们的结果以及在小鼠身上的研究结果表明，AAV1-FS344治疗可能会改善某些退行性肌肉疾病患者的肌肉质量和功能。
Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders.
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影响因子：
82.9
作者：
Ferrari, FK;Xiao, X;Samulski, RJ
通讯作者：
Samulski, RJ
影响因子：
4.8
作者：
Langley, B;Thomas, M;Kambadur, R
通讯作者：
Kambadur, R
影响因子：
82.9
作者：
Gregorevic, Paul;Allen, James M.;Chamberlain, Jeffrey S.
通讯作者：
Chamberlain, Jeffrey S.
影响因子：
82.9
作者：
Harper, SQ;Hauser, MA;Chamberlain, JS
通讯作者：
Chamberlain, JS
DOI：
10.1073/pnas.0604893104
发表时间：
2007-02-06
影响因子：
11.1
作者：
Amthor, Helge;Macharia, Raymond;Patel, Ketan
通讯作者：
Patel, Ketan