The DMD gene is made up of 79 pieces called exons. The exons link together to form a code that is read in the cells so that the protein dystrophin can be made. If there is a mutation or fault in the gene the exons no longer fit together and are not readable. The consequence is that very little or no dystrophin is made. Exon skipping drugs hide or ‘patch’ the missing piece so that the exons fit together again and can be read. A functional, although shorter, dystrophin protein is made.

Exon skipping has been shown to work in both the mdx mouse and dog models for Duchenne. 

As the exon skipping drug is designed to skip over a particular exon, different versions need to be made depending on which exons needs to be skipped. The most common mutation is around exon 51 and accounts for approximately 13% of cases of Duchenne.

Sarepta Therapeutics announced FDA accelerated approval of EXONDYS 51™ (Eteplirsen) injection, an exon skipping therapy to treat Duchenne Muscular Dystrophy (DMD) patients amenable to skipping exon 51, in September 2016.  The timeframe for the availability of EXONDYS 51 in Europe is not yet known.

WAVE Life Sciences is planning to start clinical testing of its exon 51 skipping therapy in 2017.

Stop Codon Read-Through

Another type of mutation in the DMD gene is called a nonsense mutation or premature stop codon. This type of mutation causes cells to stop synthesizing the protein dystrophin before the process is complete. This leads to a short, non-functional dystrophin protein.

Ataluren or Translarna™ is a so called stop codon read-through drug, produced by the pharmaceutical company PTC therapeutics, that has the potential to overcome nonsense mutations in the DMD gene. Ataluren is licensed in the EU for Duchenne and is an investigational product in other jurisdictions. Ataluren is an orally administered small molecule compound.