Chapter 13. Gene Therapy Approaches to Duchenne Muscular Dystrophy

Summary

Duchenne muscular dystrophy is a severe neuromuscular disorder caused by mutations in a multifunctional protein called dystrophin. The gene is extremely large with a very high rate of mutation, probably owing to its size. The protein is expressed in all normal muscle fibres. Complete correction of the morphological and immunohistochemical symptoms of muscular dystrophy have been reported in transgenic mdx mice expressing the full-length dystrophin cDNA. Phenotype reversal has also been shown in mdx mice carrying a smaller dystrophin cDNA that encodes a partially functional protein lacking part of the central rod domain. Techniques employed to transfer the dystrophin gene into cells include direct DNA injection, retroviral vectors and adenoviral vectors with varying success in animal models. Technical advances in gene transfer technology are required before gene therapy of muscular dystrophy in humans becomes possible.