Many neuromuscular diseases are genetically inherited or caused by mutations in motor function proteins. Two of the most prevalent neuromuscular diseases are Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA), which are often diagnosed during the early years of life, contributing to life-long debilitation and shorter longevity. DMD is caused by mutations in the dystrophin gene resulting in critical muscle wasting, with cardiac or respiratory failure by age 30. Lack of dystrophin protein is the leading cause of degeneration of skeletal and cardiac muscle. Corticosteroids and artificial respirators remain as the gold-standard management of complications and have significantly extended the life span of these patients. Additionally, drug therapies including eteplirsen (EXONDYS 51®), golodirsen (VYONDYS 53™), and viltolarsen (VILTEPSO®) have been approved by the FDA to treat specific types of DMD. SMA is defined by the degeneration of the anterior horn cells in the spinal cord and destruction of motor neuron nuclei in the lower brain-stem caused by SMN1 gene deletion. Loss of SMN1 protein is partly compensated by SMN2 protein synthesis with disease severity being affected by the success of SMN2 gene synthesis. Evidence-based recommendations for SMA are directed towards supportive therapy and providing adequate nutrition and respiratory assistance as needed. Treatment and prevention of complications of muscle weakness are crucial for reducing the phenotype expression of SMA. Furthermore, drug therapies including injectables such as onasemnogene abeparvovec-xioi (ZOLGENSMA®), nusinersen (SPINRAZA®), and an oral-solution, risdiplam (EVRYSDI™), are medications that have been FDA-approved for the treatment of SMA. This review discusses the current and emerging therapeutic options for patients with DMD and SMA.
Keywords: Autosomal-recessive disorder; Duchenne muscular dystrophy; Dystrophin protein; SMN1 gene; Spinal muscular atrophy.
Copyright © 2020 Elsevier Inc. All rights reserved.