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