CALEB, living With Duchenne.
Exon Skipping
Exon Skipping Strategies
Many people with Duchenne have a genetic mutation in which one or more exons (a portion of a gene) in the dystrophin gene are missing.
The dystrophin gene is the largest gene in the body and is made up of 79 exons that are linked together to form the instructions for making dystrophin. Most commonly, Duchenne is caused by a genetic mutation in which one or more exons are missing.
Due to the mutations in the dystrophin gene, the exons are not able to link together. When the exons are not linked, the body does not have the instructions to produce dystrophin.
Exon skipping involves skipping over certain mutations. If a person is amenable, it means the mutations causing their Duchenne can be “skipped over” so the body can make a shorter form of dystrophin.
Learn more about how exon skipping is intended to work:
Think of the exons like toy train cars, each with a special connection that allows one car to connect to another. The connections between cars must match, so they can connect to one another and make it possible for the train to move.
Missing exons are like missing train cars. When one or more cars are missing, the connections between them no longer line up.
If we skip over a certain exon, or car, we can restore the connection between the remaining cars to create a shorter train.
Emerging Exon Skipping Approaches
Phosphorodiamidate morpholino oligomers, or PMOs, are synthetic molecules modeled after the natural framework of RNA. Today, there are four FDA-approved PMOs. These PMOs address deletions in three exons that are common deletions in Duchenne. Additional PMO therapies are being developed to address deletions in other exons.
Investigational peptide phosphorodiamidate morpholino oligomers (PPMOs) are similar to PMO exon-skipping approaches but have an added element—a peptide (small protein) that may help the exon-skipping therapy get into cells. Clinical trials are ongoing to evaluate safety and efficacy of investigational PPMO.