Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center Box 2644, Durham, NC, USA.
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
J Physiol. 2022 Aug;600(15):3465-3482. doi: 10.1113/JP281671. Epub 2022 Jun 24.
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a deficiency in dystrophin - a structural protein which stabilises muscle during contraction. Dystrophin deficiency adversely affects the respiratory system leading to sleep-disordered breathing, hypoventilation, and weakness of the expiratory and inspiratory musculature, which culminate in severe respiratory dysfunction. Muscle degeneration-associated respiratory impairment in neuromuscular disease is a result of disruptions at multiple sites of the respiratory control network, including sensory and motor pathways. As a result of this pathology, respiratory failure is a leading cause of premature death in DMD patients. Currently available treatments for DMD respiratory insufficiency attenuate respiratory symptoms without completely reversing the underlying pathophysiology. This underscores the need to develop curative therapies to improve quality of life and longevity of DMD patients. This review summarises research findings on the pathophysiology of respiratory insufficiencies in DMD disease in humans and animal models, the clinical interventions available to ameliorate symptoms, and gene-based therapeutic strategies uncovered by preclinical animal studies.
杜氏肌营养不良症（DMD）是一种 X 连锁神经肌肉疾病，由肌营养不良蛋白缺乏引起 - 肌营养不良蛋白是一种结构蛋白，可在收缩过程中稳定肌肉。肌营养不良蛋白缺乏会对呼吸系统造成不利影响，导致睡眠呼吸障碍、通气不足以及呼气和吸气肌肉无力，最终导致严重的呼吸功能障碍。神经肌肉疾病中与肌肉退化相关的呼吸损害是呼吸控制网络多个部位中断的结果，包括感觉和运动途径。由于这种病理学，呼吸衰竭是 DMD 患者过早死亡的主要原因。目前用于治疗 DMD 呼吸功能不全的方法可减轻呼吸症状，但不能完全逆转潜在的病理生理学。这突显了开发治疗方法的必要性，以提高 DMD 患者的生活质量和延长寿命。这篇综述总结了人类和动物模型中 DMD 疾病呼吸不足的病理生理学研究结果、可改善症状的临床干预措施以及临床前动物研究揭示的基于基因的治疗策略。
