Understanding why the effectiveness of molecular patch-based therapies varies in Duchenne muscular dystrophy

Duchenne muscular dystrophy is caused by genetic changes in the dystrophin gene, which halt the production of dystrophin protein. In the absence of dystrophin, muscle cells break down and muscle tissue gets replaced by scar tissue, resulting in the weakening of the muscle. Exon-skipping therapies are an approach to treating Duchenne, which works by masking the changed regions of the dystrophin gene, allowing for production of a partial, but still functional dystrophin. One treatment relying on such an approach is golodirsen. However, while the treatment itself is effective, clinical trial results showed variable amounts of restored dystrophin in people involved in the trial, which can ultimately lead to variability in the benefits in treated people.

The main aim of this study is to understand how the changes in a person’s dystrophin gene affect the restoration of dystrophin following golodirsen treatment. The researchers think that a complex biological process, known as splicing, affects the treatment. For this reason, splicing will be the process Professor Muntoni and his colleagues will focus on in this project.

Understanding why the same treatment shows different levels of success in different people would lead to more specific clinical trial enrolments, as well as allow for more personalised and consistent drugs and treatments, with the best possible chance of success for people with Duchenne.