Duchenne Muscular Dystrophy or “DMD”, as it is commonly referred to, is a fatal genetic disorder and to date remains the number one genetic killer of children worldwide. Children born with the disease, almost all boys due to the disorder attaching itself to the X chromosome, are unable to properly manufacture the Dystrophin Protein. Dystrophin acts like a protective sheath around the muscle fibers of the body. When muscle tissue is used, by design it breaks down in order to rebuild itself into a more dense fiber. Dystrophin contains those fibers until the process is complete. Without it, the fibers are allowed to dissipate and atrophy occurs. Although great advances in the epidemiology of the disorder have been made in the past ten years, a treatment or cure has remained unobtainable. Various avenues of research exist worldwide and include many ground-breaking technologies and medical firsts.
Several gene-based therapies have shown substantial evidence of altering the disease and continue to be studied in several countries. Areas of study include:
- Exon Skipping, a version of therapy where the damaged RNA is spliced together circumventing the missing exons so that complete replication of the necessary protein can occur
- Antisense Oglionucleotide Therapy, where a synthetic form of DNA is used as a “band aid” for the damaged DNA so that a viable RNA is produced
- Premature Stop Codon Read Through which uses a specific family of antibiotics (PTC-124) to cause the RNA to ignore the incorrect “stop” command in order to produce a complete protein sequence
These therapies have all shown significant results in clical models and in early phase efficacy trials. With further development, they offer the most hope in finding a lifesaving treatment.
Cell based therapy has long been thought to be the easiest way to propagate normal functioning Dystrophin. The idea of “repopulating” damaged muscle fiber with fully functional cells in order to either fuse them to damaged muscle or to create new usable muscle tissue was initially thought to be the easiest way to treat DMD. Transplantion of the repair matter has been difficult to achieve. Duchenne effects all muscle tissue through out the body, therefore making a means of delivery difficult. In recent years, clinitians involved in Duchenne research have discovered that the use of “Vector” or empty virus as the means for mass transportation of treatment matter could solve this issue. Research in this area continues and the various developments occurring as a result of these efforts prove to be vital in solving the Duchenne disorder.
Utrophin upregulation is another area of study and involves increasing levels of naturally occurring Utrophin protein in order to substitute the damaged or incomplete Dystrophin. Utrophin is the predominant protein in humans at birth and is slowly replaced with Dystrophin within the first year of life. Our bodies use Utrophnin through out life as the connecting protein between nerve ending tissue and muscle fiber. Scientist believe that through upregulation of this protein, a substitution of Dystrophin is possible and recent evidence uncovered by this study has shown that only a 30% increase in either the Dystrophin or Utrophin protein is sufficient for sustaining viable muscle tissue. Various compounds are being studied using pioneering technology developed to speed up the screening process of millions of drug and compound combinations. This pioneering technology was developed by PTC Theraputics in collaboration with Parent Project MD (a Duchenne support and research foundation).
As with most other forms of technology-aided research, opportunities and possibilities for new developments occur at a far faster rate in today’s DMD world than ever before. However, as with most forms of medical research, the Federal Government has been slow to act with little or no substantial funding for on going research. Due to the direct involvement and persistent efforts of certain Duchenne focused organizations such as Parent Project MD and Charley’s Fund, progress has been made in both government funding and legislative support of DMD research. This progression will only continue with the added support and financial resources made available by foundations through out the world such as Two Smiles One Hope.