Duchenne muscular dystrophy: Current treatment and emerging exon skipping and gene therapy approach

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder that causes debilitating muscle weakness and atrophy due to a loss of the dystrophin protein. Patients with DMD are commonly diagnosed at about 3-5 years of age and progressively decline until complications of the disease often result in death at about 20 years of age. While there is no current cure for DMD, several treatment options focus on improving the quality of life and slowing progression of symptoms associated with the disease. The current treatment for DMD is glucocorticoids and physical therapy. Respiratory therapy, cardiac management, bone health maintenance, orthopedic interventions, and dietary considerations are also utilized in managing DMD patients. Emerging therapeutic approaches include gene transfer therapy using adeno-associated virus (AAV) vectors, and exon skipping agents. Both approaches have been shown to be relatively safe, with few significant side effects. Even though exon skipping agents produce a smaller dystrophin protein, they effectively preserve a significant portion of its function. Exon skipping agents have clinical advantages over traditional therapies, such as corticosteroids, because they slow the progression of DMD in addition to relieving symptoms. This review discusses the pathogenesis of DMD and explores the current treatment options as well as new and emerging therapies.

Keywords: Duchenne muscular dystrophy; Dystrophin protein; Emerging therapies; Exon skipping agents; FDA approved therapies; Gene therapy.