Therapeutic prospects to treat skeletal muscle wasting in COPD (chronic obstructive lung disease).
Chronic obstructive pulmonary disease (COPD) is an incurable group of lung diseases characterised by progressive airflow limitation and loss of lung function, which lead to profound disability. It is mostly caused by cigarette smoke. Although COPD is one of the most prevalent diseases worldwide and its incidence is increasing, current therapies do little to improve the condition. Much current research focuses on strategies to halt the accelerated rate of decline in lung function that occurs in the disease. However, as most symptoms occur when the lungs are already extensively and irreversibly damaged, it is uncertain whether an agent able to slow or halt decline in lung function would actually provide relief to COPD patients. As lung function worsens, systemic comorbidities contribute markedly to disability. Loss of lean body mass (skeletal muscle) has recently been identified as a major determinant of disability in COPD and an independent predictor of mortality. In contrast to lung structure damage, skeletal muscle retains regenerative capacity in COPD. In this review, we discuss mechanisms of wasting in COPD, focusing on therapeutic strategies that might improve the health and productive life expectancy of COPD patients by improving skeletal muscle mass and function. Single or combination approaches exploiting the suppression of procatabolic inflammatory mediators, inhibition of ubiquitin ligases, repletion of anabolic hormones and growth factors, inhibition of myoblast apoptosis, remediation of systemic oxidative stress and promotion of repair, and regeneration via stimulation of satellite cell differentiation hold considerable therapeutic promise.
Hansen
Michelle J
MJ
Lung Disease Research Laboratory, Department of Pharmacology, Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Victoria 3010, Australia. mjhansen@unimelb.edu.au
Gualano
Rosa C
RC
Bozinovski
Steve
S
Vlahos
Ross
R
Anderson
Gary P
GP
D000818:Animals; D006728:Hormones / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000473:pathology; D019282:Wasting Syndrome / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology
D006728:Hormones