Duchenne muscular dystrophy (DMD) is one of the most common and devastating types of muscular degeneration and results in progressive muscle weakness, starting at young age. It is a genetic disorder affecting approximately 1 in 3,500 to 5,000 new-born boys, depriving sufferers first of their childhood and eventually their lives. DMD pathology is driven by a lack of dystrophin and resulting muscle cell weakening and fibrosis.
DMD affects approximately 20,000 boys and young men in the United States and approximately 20,000 to 30,000 boys and young men in Europe. It is estimated that DMD causes an economic burden of above $1 billion per year in the United States.
Unable to live “normal” lives because of progressive and irreversible muscle loss, patients typically lose the ability to walk by their early teens and succumb to respiratory or heart failure in their 20s to 30s. Duchenne is 100 percent fatal.
While respiratory failure has historically been the main cause of mortality in DMD, the use of steroids and respiratory assist devices has led to an extended life expectation and shift in driver of mortality – most young men with DMD today die from heart failure. Cardiomyopathy, weakness of the heart muscle, occurs by age 18 in 90 percent of male DMD patients.
DMD is an X-linked disease that is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein which is critical for stabilizing muscle cell membranes, causing muscle degradation and fibrosis.
Therapeutic treatment includes corticosteroids which aim to reduce inflammation that exacerbates muscle fibre damage and as a result may improve muscle strength, but have insufficient efficacy and significant side effects including weight gain, reduced bone density and growth retardation. Available treatments do not replenish the lack of dystrophin or address the augmenting fibrosis of muscle tissue.
Our research suggests sPIF may have the potential to promote myofiber growth, muscle differentiation and muscle regeneration and may block fibrosis via effects on Th1/ Th2 cells, M1/ M2 macrophages and Tregs. Preclinical work has shown intriguing effects on clinically relevant endpoints in MdX mice, the standard model of DMD.