Exon-skipping drug pulls ahead in muscular dystrophy field

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...

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...

Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping.

Nonsense mutations outside the splicing consensus sequence have been reported to cause skipping of the nonsense-containing exon in several human diseases. We describe, for the first time, nonsense-mediated exon skipping in the laminin alpha2 (LAMA2) gene. Two siblings from a consanguineous family had altered expression of the laminin alpha2 chain and moderate clinical manifestations. In both we...

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic diseases worldwide, caused by mutations in the dystrophin (DMD) gene. Exon skipping employs short DNA/RNA-like molecules called antisense oligonucleotides (AONs) that restore the reading frame and produce shorter but functional proteins. However, exon skipping therapy faces two major hurdles: limited applicability (up to...