Introduction

Since the discovery of the gene responsible for DMD (Koenig et al. 1987), and the subsequent identification of the genes responsible for other forms of muscular dystrophy, there has been intense effort in the development of methods for restoring gene function, commonly referred to as gene therapy (Foster et al. 2006; Cossu and Sampaolesi 2007; Muntoni and Wells 2007). The availability of a range of spontaneous and engineered animal models has allowed extensive pre-clinical testing (e.g., Wells and Wells 2005; Banks and Chamberlain 2008; Spurney et al. 2009;

Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Hammersmith Hospital Campus, Imperial College London, Room E512, Building 560/ Burlington Danes, 160 Du Cane Road, London, W12 ONN, UK e-mail: [email protected]

DOI 10.1007/978-1-4419-1207-7_16, © Springer Science+Business Media, LLC 2010

Willmann et al. 2009) and the subsequent translation of many of these novel therapies into early clinical trials. A key step has been the pre-clinical demonstration of the potential for systemic administration and delivery of therapeutic agents to all of the affected muscles. Regional or systemic treatment will be essential as local treatment by intramuscular injection, while useful for first in man studies, results in very limited diffusion from the site of injection and therefore, clinical benefit is highly unlikely. Examples of pre-clinical data for approaches now in clinical trial include the use of replication-deficient viral vectors to transfer recombinant versions of the affected gene, the transfer of recombinant genes in simple bacterial plasmids, the transfer of normal or recombinant genes via cell transfer, and the use of antisense oligonucleotides to modify the splicing of the primary transcript to generate mRNA and by excluding specific exon(s) to restore the reading frame in frame shift mutations.

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