• Open Access

Problems and solutions in myoblast transfer therapy

Authors

  • Gayle M. Smythe,

    Corresponding author
    1. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, California, USA
    Search for more papers by this author
  • Stuart I. Hodgetts,

    1. Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth, Western Australia, Australia
    Search for more papers by this author
  • Miranda D. Grounds

    1. Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth, Western Australia, Australia
    Search for more papers by this author

*Correspondence to: Dr. Gayle SMYTHE Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, California 94304-5235, USA. Tel.: (650) 493 5000 (extension 63731), Fax: (650) 858 3935 E-mail: gaylesmythe@hotmail.com

Abstract

Duchenne muscular dystrophy is a severe X-linked neuromuscular disease that affects approximately 1/3500 live male births in every human population, and is caused by a mutation in the gene that encodes the muscle protein dystrophin. The characterization and cloning of the dystrophin gene in 1987 was a major breakthrough and it was considered that simple replacement of the dystrophin gene would ameliorate the severe and progressive skeletal muscle wasting characteristic of Duchenne muscular dystrophy. After 20 years, attempts at replacing the dystrophin gene either experimentally or clinically have met with little success, but there have been many significant advances in understanding the factors that limit the delivery of a normal dystrophin gene into dystrophic host muscle. This review addresses the host immune response and donor myoblast changes underlying some of the major problems associated with myoblast-mediated dystrophin replacement, presents potential solutions, and outlines other novel therapeutic approaches.

Ancillary