1. Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Richards A-601, Philadelphia, Pennsylvania 19104-6085, USA
2. Musculoskeletal Sciences Department, Wyeth Research, Cambridge, Massachusetts 02140, USA
3. Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
4. These authors contributed equally to this work

Correspondence to: Tejvir S. Khurana¹ Correspondence and requests for materials should be addressed to T.S.K. (e-mail: Email: tsk@mail.med.upenn.edu).

Abstract

Mice^{1, 2} and cattle³ 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- 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, 5, 6, 7, 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.