Breathing in Duchenne muscular dystrophy: translation to therapy.
Breathing in Duchenne muscular dystrophy: translation to therapy.
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DOI：
10.1113/jp281671
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发表时间：
2022-08
影响因子：
5.5
通讯作者：
ElMallah, Mai K.
中科院分区：
文献类型：
--
作者：
Mhandire, Doreen Z.;Burns, David P.;Roger, Angela L.;O'Halloran, Ken D.;ElMallah, Mai K.
Duchenne肌营养不良症(DMD)是一种X连锁的神经肌肉疾病，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，在收缩时稳定肌肉。营养不良蛋白缺乏对呼吸系统造成不利影响，导致睡眠呼吸障碍、呼吸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。神经肌肉疾病中肌肉变性相关的呼吸损害是呼吸控制网络多个部位中断的结果，包括感觉和运动通路。由于这种病理，呼吸衰竭是DMD患者过早死亡的主要原因。目前可用于治疗DMD呼吸功能不全的治疗方法可以减轻呼吸道症状，但不能完全逆转潜在的病理生理机制。这强调了开发治疗方法的必要性，以提高DMD患者的生活质量和寿命。本文综述了在人类和动物模型中DMD疾病呼吸功能不全的病理生理学方面的研究成果，可用于改善症状的临床干预措施，以及临床前动物研究发现的基于基因的治疗策略。DMD(Duchenne肌营养不良症)呼吸功能不全的治疗策略综述目前临床使用的治疗方案只减轻呼吸道症状，而不能逆转与DMD相关的呼吸功能不全的基本病理。正在进行的临床前和临床研究旨在开发既能提高DMD患者的生活质量，又能延长患者寿命的根治疗法。腺病毒相关病毒，PPMO-多肽偶联的磷二酸吗啉低聚物
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a deficiency in dystrophin - a structural protein which stabilizes 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. Summary of the therapeutic strategies for respiratory insufficiency in DMD (Duchenne muscular dystrophy). Treatment options currently in clinical use only attenuate respiratory symptoms without reversing the underlying pathology of DMD-associated respiratory insufficiencies. Ongoing preclinical and clinical research is aimed at developing curative therapies that both improve quality of life and longevity of DMD patients. AAV – adeno-associated virus, PPMO - Peptide-conjugated phosphorodiamidate morpholino oligomer