Duchenne muscular dystrophy (DMD) is a lethal muscle disease which is caused by non functional dystrophin protein. Normal dystrophin gives a proper structure to our muscle and enables us to perform physical activities, such as walking… and dancing!
The dystrophin protein is encoded by the DMD gene, which consists of arrays of exons (E) and introns (I). To make dystrophin protein, the introns have to be spliced out by the spliceosome (pink). The exons are then joined together and the amino acids (AA) are synthesized.
When there is a mutation (STOP) in the DMD gene, the dystrophin protein cannot be synthesized properly and therefore not functional. This non functional dystrophin makes the muscle weak, more prone to damage and eventually degenerate. Currently there is no curative treatment for this disease.
In our lab, we are working on an approach called “exon skipping”. We try to correct this faulty gene using a molecule called antisense oligonucleotides (AON, green). What does it do? The AON is designed to target, bind and mask/hide the mutated exon. The hidden exon will be treated as an intron by the spliceosome, and spliced out together with the other introns. Hence the AON is a “skip man” :) Dystrophin produced after exon skipping will be shorter, but should be sufficient for the affected patient to carry out physical activities to a certain extent.
This exon skipping approach is now in advanced clinical trial, but there are still more questions need to be answered. For example, how to target the AON more efficiently to the entire body, what is the minimum level of dystrophin needed, can the AON be combined with any
other drugs to help improve the muscle quality of the patients, and many more.
To answer these, we have a mix of biologists and bioinformaticians working closely together. All of us share passions to DMD research and… definitely to dancing :)