Understanding the Biology of a Rare Genetic Disease

Duchenne muscular dystrophy (DMD) is a devastating inherited disorder that causes muscle wasting in boys. Symptoms begin early in childhood (around 3-5 years old) and progress quickly. Those afflicted with DMD are usually wheelchair-bound by their teens and often die from heart or lung failure by their mid-20s.

DMD is caused by mutations in the gene that produces dystrophin, a connective protein that strengthens muscle fibers. Although the genetic cause of DMD has been known for over 30 years, we still do not fully understand how loss of dystrophin leads to muscle deterioration.

There is no cure for DMD and monitoring disease progression and drug response in clinical trials is difficult. The primary measure in most trials is the six-minute walking distance which excludes very young children as well as older patients who can no longer walk. More accurate and objective measures of DMD are essential for assessing efficacy and speeding FDA approval of new therapies.

To identify biomarkers for DMD, the SOMAscan assay was used to measure protein levels in serum samples from Duchenne patients and age-matched healthy controls. Forty-four proteins showed significant changes (24 increased and 20 decreased) in patients with DMD. The proteins link to disease processes such as muscle fiber leakage, fibrosis, inflammation and muscle degeneration.

Many of the DMD protein markers were at their highest levels in the youngest patients and then decrease with age as muscles atrophy. These results suggest that significant muscle damage is occurring at a very early age (before 4 years). Protein measurements could offer a minimally invasive way of monitoring DMD during infancy, when interventions are likely to have the biggest impacts.

Hathout, Y et al. (2015) Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 112(23): 7153-7158.
http://www.pnas.org/content/112/23/7153.full.pdf?with-ds=yes