Injection of DMD gene is the initial approach for gene therapy strategy to envisage. A truncated gene is encapsuled in a recombinant adeno-associated virus and injected into patients [Gregorevic et al., 2006]. Then, a functional truncated dystrophin is produced by the patient's cells. The size of the delivered gene is limited by the vector size and therefore reduced DMD genes (mini- or micro-gene) have been constructed to be encapsulated in recombinant adeno-associated viruses. These mini- or micro-genes may be able to produce partially functional internally truncated dystrophins such as those observed in BMD.

genic therapy
Exemple of gene therapy with a truncated DMD gene inserted.

Exon skipping therapy is one of the most promising experimental therapies for Duchenne Muscular Dystrophy [Beroud et al., 2007], [Arnett et al., 2009]. This skipping restores a true reading frame leading to the synthesis of a dystrophin deleted for part of the central coiled-coil region as observed in BMD patients. This strategy should transform a DMD patient into a BMD patient [Goyenvalle et al., 2004, Aartsma-Rus et al., 2002]. Antisense oligonucleotides (AO) are used to alter gene expression by skipping one or more exons in the final transcript with different associated strategies [Wilton & Fletcher, 2008, Goyenvalle et al., 2010].
However, this strategy has some limitations. AOs can be used to skip all single exons except the first and last exons. The exon skipping strategy is mutation-specific but some exon skipping strategies could be applicable to large groups of patients [Aartsma-Rus et al., 2009]. The mode of administration is not yet well defined to restore dystrophin expression particularly in cardiac muscle.

Cell therapy is an alternative therapy with the aim of restoring a pool of normal muscle cells in the skeletal or heart muscles. First, a transplantation of adult myoblasts is performed but these cells have only a limited survival time. Now, dissemination of skeletal muscle precursors being studied.

exon skipping
Exemple of exon skipping by skipping exon 51 on a deletion from exons 45 to 50