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From Roberts 2001, 10.1186/gb-2001-2-4-reviews3006

Dystrophin is the largest known human gene, covering about 2.4 million basepairs. The gene has 79 exons, which when spliced together yield a relatively modest relatively modest 425 kDa protein–still huge, but perhaps less than one might expect given its genomic sequence. It connects the actin-based cytoskeleton of muscle fibres, through the cell membrane, to the extracellular matrix. Such a situation makes it critical for muscle development and function, and indeed, mutations in dystrophin cause muscular dystrophy (MD).

What is curious about dystrophin is that relatively minor mutations cause severe forms of the disease. This is because they introduce frame-shifts in the coding sequence, resulting in a messed up protein. Antisense-based “exon-skipping” strategies have been proposed to treat MD (see 10.1093/hmg/10.15.1547 for example), and there have even been a couple of clinical trials: one reported in the New Engl J Med in April; and another, again using antisense oligos, in The Lancet today. Skipping troublesome exons allows the protein to be expressed normally, albeit slightly shorter than normal. The truncated protein can function about as well as the full length, wild type version.

The most recent trial treated 19 Duchenne MD (DMD) patients with an antisense morpholino oligo called AVI-4658, which induces skipping of dystrophin exon 51. The patients had 12 weekly infusions with the antisense oligo, and seven of the patients increased their dystrophin protein levels.

The improvement appears quite modest, and this particular form of the treatment can only potentially help around 13% of DMD patients, but these results are very encouraging indeed. You can read more about the research at the BBC.