It is an incredibly exciting time in the Duchenne and Becker muscular dystrophy community with so many potential therapies in the pipeline. Many of these therapies are mutation-specific, meaning they will only work for individuals with certain mutations in their Duchenne gene.
This brief explanation may help you to understand if you or your child may be a candidate for one of the mutation-specific therapies in development.
If you’ve never had genetic testing or if you need repeat genetic testing, remember that our Decode Duchenne program provides FREE genetic testing to eligible individuals. If you have questions, please contact one of Parent Project Muscular Dystrophy’s board-certified genetic counselors.
Two key types of mutation specific therapies
There are currently two types of mutation-specific therapies in clinical trials for Duchenne: nonsense mutation suppression and exon skipping.
Nonsense mutation suppression
Individuals with Duchenne who have a nonsense mutation may be candidates for nonsense mutation read-through. A nonsense mutation is a single change in the Duchenne gene that creates a “premature stop codon”, which basically stops production of the dystrophin protein too early in the process and results in a non-functioning protein. Some (but not all) genetic test reports will state if the mutation is a nonsense mutation. Learn more about nonsense mutation read-through.
Individuals with Duchenne who have certain “out-of-frame” deletions may be candidates for exon skipping. Out-of-frame deletions usually result in little or no dystrophin protein which usually means the individual will have Duchenne. With exon skipping, one or more of the exons bordering the deletion are also skipped, with the purpose of turning the “out-of-frame” deletion into an “in-frame” deletion. In-frame deletions usually result in some dystrophin protein production. However, the impact that exon skipping will have on an individual’s disease progression has not been clearly demonstrated. Learn more about exon skipping.
Determining if a deletion is amenable to exon-skipping therapies
There are more than 150 different deletions of one or more exons in the dystrophin gene that can cause Duchenne muscular dystrophy. Exon-skipping research is at different stages for many of these deletions. Exon-skipping therapy for some deletions has reached clinical trials. This group includes deletions that are amenable to skipping exons 51, 53, 45, and 44. For other deletions, however, exon-skipping therapy is only theoretical. This group includes deletions that would need more than one exon skipped or that are in specific regions of the gene that may not be correctable with exon-skipping.
If you know your/your child’s genetic change (mutation) is an exon deletion, our educational Exon Deletion Tool can help you understand if you/your child may be a candidate for an exon skipping therapy. Table 1 (below) also shows the deletions that would be amenable to the exon-skipping therapies that are furthest in the development pipeline. It does not represent a complete list of all deletions that may be treatable with exon-skipping. If you have questions about your genetic results or mutation-specific therapies, contact one of Parent Project Muscular Dystrophy’s board-certified genetic counselors.
Looking to the future: other types of technologies
Researchers are studying other technologies that may provide more mutation-specific therapies in the future. One of these technologies is called CRISPR/Cas9. The goal of this technique is to edit the gene itself to correct the mutation causing disease. CRISPR/cas9 is being explored for many conditions, but is not ready for clinical trials yet.
Parent Project Muscular Dystrophy offers many ways to stay up to date on research advancements and clinical trials:
Table 1: Duchenne gene deletions amenable to certain exon skipping therapies
|Exon 51 Skip-amenable||Exon 53 Skip-amenable||Exon 45 Skip-amenable||Exon 44 Skip-amenable||Exon 50 Skip-amenable||Exon 52 Skip-amenable||Exon 55 Skip-amenable|
|(13% of Duchenne population)||(8% of Duchenne population)||(8% of Duchenne population)||(6% of Duchenne population)||(4% of Duchenne population)||(4% of Duchenne population)||(2% of Duchenne population)|