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Review
. 2022 Aug;600(15):3465-3482.
doi: 10.1113/JP281671. Epub 2022 Jun 24.

Breathing in Duchenne muscular dystrophy: translation to therapy

Doreen Z Mhandire  1 , David P Burns  2 , Angela L Roger  1 , Ken D O'Halloran  2 , Mai K ElMallah  1
Affiliations
Review

Breathing in Duchenne muscular dystrophy: translation to therapy

Doreen Z Mhandire et al. J Physiol. 2022 Aug.

Abstract

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.

Keywords: AAV gene therapy; Duchenne muscular dystrophy (DMD); control of breathing; dystrophin; respiratory insufficiency; respiratory muscle.

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

Figures

Figure 1:
Figure 1:
Sleep disordered breathing in DMD is a result of pathology in muscles and nerves that control respiration. Obstructive sleep apnoea results, which is characterised by reduced responsiveness to chemoreceptor challenge, upper airway collapse, and hypoxaemia.
Figure 2:
Figure 2:
Extensive pathology in both muscular and neural components of the respiratory system in DMD disease. The widely spread pathology leads to respiratory failure and premature death of DMD patients.
Figure 3:
Figure 3:
Ventilatory function loss ensuing diaphragm muscle pathology in an mdx mouse, DMD dog model and DMD patient. NIPPV - Nasal intermittent positive pressure ventilation, DMD – Duchenne muscular dystrophy
See this image and copyright information in PMC

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