Duchenne muscular dystrophy (DMD) is the most common lethal genetic disease of childhood. Early on, children with DMD have difficulty running, jumping, and walking up steps and are usually wheelchair bound by the age of twelve.
What causes it? A missing gene that prevents the formation of dystrophin. Dystrophin is a key protein that protects the muscle from injury. Without dystrophin, young boys experience skeletal muscle deterioration and become progressively more disabled over time, often dying from respiratory or heart failure before their twenty-fifth year. It is more common in boys because of its X-linked inheritance.
Why the heart, that’s not a skeletal muscle? Dystrophin has an important role in stabilizing the cell membrane of both skeletal and cardiac muscle cells or “myocytes.” Sadly, this means heart failure also occurs in those with Duchenne muscular dystrophy.
What medications have been used to treat DMD? In the past, the only medication shown to be effective in delaying the progression of illness are corticosteroids. Corticosteroids (prednisone or Solu-medrol) have been shown to increase muscle strength and potentially prolong walking time while slowing the progression of cardiomyopathy. But, long term steroid use has problems.
What is eteplirsen and how might it help? Now Exondys 51 (eteplirsen) has been approved, with a fight by the FDA. As one of the first examples of precision genetic medicine, how it works is complicated. Eteplirsen works by gene transfer, resulting in a corrected version of the gene which is then able to produce dystrophin.
Will eteplirsen work in all patients with DMD? Maybe not, as it is only intended for DMD patients with some specific DMD mutations.
How does eteplirsen help patients with DMD? Recent results of four year studies showed that only two of twelve eteplirsen-treated boys have lost the ability to walk, compared with ten of eleven in the control group (those who did not receive eteplirsen).
Why was it hard to get Eteplirsen approved? Well, because DMD is a rare disease (and as a result, does not have a loud advocacy group). This medicine is also highly personalized and expensive. Initially the FDA wanted more and longer studies to show that it is effective, but a group of 36 leading Duchenne experts provided written commentary, and patients themselves showed up to beg for approval. It worked.
Accelerated approval, with more studies to come. For rare diseases with small populations to study, the traditional path to approval for new treatments is difficult. Because of this, approval of eteplirsen was fast-tracked, but trials on its effectiveness and safety will be ongoing. For now, it’s here to stay.