Treatment of Duchenne muscular dystrophy at the mRNA level

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease and so far, the treatment of DMD has not yet been established. Here, gene therapy is proposed as a novel treatment for DMD whereby the correction of the translational reading frame transforms severe DMD into the milder Becker muscular dystrophy. Based on the molecular analysis of dystrophin Kobe where the presence of an intra-exon deletion caused exon skipping during splicing, a part of the exon 19 sequence of the dystrophin gene was found to function as a splicing enhancer sequence, a sequence necessary for proper splicing. When oligonucleotides complementary to this sequence were added to the culture medium of lymphoblastoid cells, exon 19 skipping was specifically induced. This raises the possibility of a new therapeutic approach for DMD where dystrophin pre-mRNA splicing can be modulated by an oligonucleotide against a splicing enhancer sequence to produce an in-frame transcript that is able to produce truncated dystrophin. One natural example of this transformation is described.