Duchenne Muscular Dystrophy (DMD)

In patients with DMD, inflammatory changes in the muscle, damage to the muscle cell membrane and uncontrolled flow of calcium ions result in compromised muscle function.5 Over time, this damage leads to progressive muscle weakness and loss of muscle tissue including a decline in skeletal muscle-, respiratory muscle- and cardiac muscle- function.^4,5 Treatment with corticosteroids and supportive care are the current standard of care for treating DMD^6,7,8; however, chronic corticosteroid treatment is associated with significant side effect burdens. While variable amongst DMD patients, the significant stages in the disease course are inability to ambulate independently, feed oneself, respiratory insufficiency requiring assisted ventilation, and cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure.

Signs and symptoms of DMD

In early stages of DMD, generalized muscle weakness in the arms and legs, especially in the proximal muscle groups (such as the hip muscles and the shoulder muscles) is most prominent. Boys with DMD are usually “late walkers” (after 14 months of age). In young boys, the very first sign of the disease is the presence of large calves (calf pseudohypertrophy), accompanied by elevated levels of creatinine kinase (CK). Some infants may present with delayed motor milestones. Patients with DMD may find it difficult to get up from the floor (also known as Gower’s sign), climb up steps, or run. Usually by age 12, most DMD patients begin using a wheelchair.⁹ In late stages of DMD, patients lose their ability to walk independently (loss of ambulation), feed themselves, breath normally (respiratory insufficiency), and they also develop heart dysfunction (cardiomyopathy).

Diagnosis

A diagnosis of DMD is initially suspected based on signs and symptoms in the presenting male child. Clinical symptoms during a physical examination, the pattern of muscle weakness and family history are critical in this process. Typically, electromyography reveals a myopathic pattern, and laboratory evaluation shows an elevated CK level. While the absence of dystrophin protein may be demonstrated by muscle biopsy-based evaluation, definitive diagnosis is made by dystrophin gene testing.

Treatment

Currently, corticosteroids are the mainstay of pharmacologic treatment in DMD. While chronic treatment with corticosteroids has many adverse effects associated with them, it has been shown to delay the loss of ambulation. A DMD gene therapy was recently approved for the treatment of DMD in a select age group of patients¹⁰.