Accurate quantification of dystrophin mRNA and exon skipping levels in Duchenne Muscular Dystrophy

Exon skipping therapy for Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is caused mostly by internal deletions in the gene for dystrophin, a protein essential for maintaining muscle cell membrane integrity. These deletions abrogate the reading frame and the lack of dystrophin results in progressive muscle deterioration. DMD patients experience progressive loss of ambulation, followed by a need for assisted ventilation, and eventual...

Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy.

We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection. We now show th...

Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish

Duchenne muscular dystophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene. By utilizing antisense oligonucleotides, splicing of the dystrophin transcript can be altered so that exons harbouring a mutation are excluded from the mature mRNA. Although this approach has been shown to be effective to restore partially functional dystrophin protein, the level of d...

AON-Mediated Exon Skipping for Duchenne Muscular Dystrophy

Less is more: therapeutic exon skipping for Duchenne muscular dystrophy.

www.thelancet.com/neurology Vol 8 October 2009 873 Duchenne muscular dystrophy (DMD) is a lethal Xlinked progressive muscle-wasting disease caused by premature truncation of the translation of DMD mRNA into dystrophin. Owing to improved respiratory support and treatment with steroids, patients can now survive into early adulthood, which is one or two decades longer than they could survive witho...