What is Exon Skipping in laymans speak?
Exon skipping is a potential treatment for Duchenne muscular dystrophy. It would not cure the disease, but might greatly reduce the symptoms and progression in those who have the kind of mutation it targets. The exact substance used will depend on the location of that patient’s mutation within the gene. There are many kinds of mutations, and many variations in how they affect people. Several different approaches to exon-skipping are being explored by teams all over the world.
Genes are made up of "bases"; there are 2.2 million of them in the dystrophin gene (it’s a huge gene). An exon is a "phrase" in a gene; there are 79 of them in the dystrophin gene, each made up of a chain of base pairs. As DNA is read by the body, each three-letter group of bases codes for a particular amino acid, or tells the process to stop, or may not mean anything.
If an exon is missing, and the number of bases that are affected interrupts a code, the translation for everything downstream of that is nonsense. If the genes said "THE CAT WAS TOO FAT," and the "W" was missing, the sentence would read, "THE CAT AST OOF AT." This is referred to as "out-of-frame," and the resulting protein is useless.
A mutation can cause either Duchenne (the very severe form, often caused by an out-of-frame deletion) or Becker (the milder form, often caused by an in-frame deletion) muscular dystrophy. In exon skipping, one or more adjacent exons is skipped, resulting in a shorter, but functional protein. If, using the example above, the "AS" in "WAS" is skipped, we get, "THE CAT TOO FAT." It’s not a perfect sentence, but it’s in-frame and we can get by with it. Theoretically, this will convert the Duchenne dystrophy into the Becker form. You can easily Google those diseases for more information.
This is one form of research which will hopefully provide a treatment for MD in the next few years. There are 79 exons (words) which form the message from the brain to muscle. With Duchenne boys 1 or 2 of these are faulty. The message stops and dystrophin does not get to the muscles. Researchers in this field are confident that by placing a “band-aid” correctly the message will “skip over” the faulty exons and dystrophin can start to enter the muscles. MDEX Consortium in London have been targetting EXON 51 (20% of boys have EXON 51) and have reached the clinical testing stage on this. They have recently chosen another researcher to target 6 other exons. Unfortunately Exon 68 – which is the faulty exon in our boys – was not chosen. However, a pioneer of Exon Skipping, Professor Steven Wilton at the University of Western Australia has agreed to target EXON 68 and other mutations not being targeted in London. This work is already under way and our group has pledged £40,000 per year to set
