Breathing in Duchenne muscular dystrophy: translation to therapy.

Autor: Mhandire DZ; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center Box 2644, Durham, NC, USA., Burns DP; Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland., Roger AL; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center Box 2644, Durham, NC, USA., O'Halloran KD; Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland., ElMallah MK; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center Box 2644, Durham, NC, USA.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2022 Aug; Vol. 600 (15), pp. 3465-3482. Date of Electronic Publication: 2022 Jun 24.
DOI: 10.1113/JP281671
Abstrakt: 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.
(© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)
Databáze: MEDLINE
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