Functional improvement of dystrophic muscle by myostatin blockade

被引:647
作者
Bogdanovich, S
Krag, TOB
Barton, ER
Morris, LD
Whittemore, LA
Ahima, RS
Khurana, TS
机构
[1] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA
[3] Wyeth Res, Musculoskeletal Sci Dept, Cambridge, MA 02140 USA
[4] Univ Penn, Sch Med, Div Endocrinol, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
D O I
10.1038/nature01154
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mice(1,2) and cattle(3) with mutations in the myostatin (GDF8) gene show a marked increase in body weight and muscle mass, indicating that this new member of the TGF-beta superfamily is a negative regulator of skeletal muscle growth. Inhibition of the myostatin gene product is predicted to increase muscle mass and improve the disease phenotype in a variety of primary and secondary myopathies. We tested the ability of inhibition of myostatin in vivo to ameliorate the dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD)(4-8). Blockade of endogenous myostatin by using intraperitoneal injections of blocking antibodies for three months resulted in an increase in body weight, muscle mass, muscle size and absolute muscle strength in mdx mouse muscle along with a significant decrease in muscle degeneration and concentrations of serum creatine kinase. The functional improvement of dystrophic muscle by myostatin blockade provides a novel, pharmacological strategy for treatment of diseases associated with muscle wasting such as DMD, and circumvents the major problems associated with conventional gene therapy in these disorders.
引用
收藏
页码:418 / 421
页数:5
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