Dr Ahlke Heydemann, Associate Professor and Director of Medical School Curriculum at University of Illinois, Chicago explains Duchenne muscular dystrophy (DMD), focussing on the issue of correcting the dystrophin gene
Duchenne muscular dystrophy (DMD) is an inherited progressive disease that affects skeletal, diaphragm and cardiac muscles. The pathology initiates with muscle weakness, particularly noticeable on the leg muscles of the young – two to three-year-old – boys. The dystrophin gene is located on the X-chromosome; therefore, it is sex-linked and only boys get the full disease. Women are carriers and can develop cardiomyopathy much later in life. As time goes on, the skeletal muscles continue to weaken, and corticosteroid treatments are initiated, usually at around six years of age.
A few years later, night-time assisted ventilation and then prophylactic ACE inhibitors for the maintenance of respiratory and cardiac function, respectively, are added to the treatment regimen. These combined treatments have extended the quality and quantity of the patients’ lives, but more effective treatments or even cures are still urgently required. Within MD, there is some relationship between the specific mutation in the dystrophin gene and the protein levels of dystrophin and the severity of the disease.
The mildest cases are classified as Becker MD (BMD). These mild cases reveal that a relatively low expression level of dystrophin – only 20 to 40 % of normal levels – is required to establish a mild disease course. This very important trait can be utilised to set a reasonably achievable goal for a highly beneficial and successful therapy.