Work group of DZL researcher identifies target molecule for the treatment of chronic obstructive pulmonary disease (COPD).
It is mainly caused by cigarette smoke and air pollution and is among the major global causes of death: chronic obstructive pulmonary disease (COPD). Patients affected by this disease are chronically ill, physically severely limited, and have a significantly reduced life expectancy. There is currently no treatment to stop the progression of this life-threatening disease or even reverse lung damage. Highly reactive molecules, called oxygen radicals, have been suspected to play a substantial role in the destruction of lung tissue (pulmonary emphysema) in COPD for quite some time now. However, it has not yet been possible to identify their source and block their development. The work group of DZL researcher Prof. Dr. Norbert Weißmann at the excellence cluster “The Cardio-Pulmonary Institute (CPI)” of Giessen University (JLU) has already demonstrated in previous studies that a molecule resulting from the reaction of nitrogen monoxide with oxygen radicals causes the disease. Now the research team has also explored the cellular source of the oxygen radicals. The results were published in the renowned scientific journal “Nature Metabolism”.
In their current study, the researchers demonstrated that a cellular enzyme producing oxygen radicals (called NADPH oxidase with the subunit NoxO1) is the major producer of the pathogenic oxygen radicals. “This enzyme drives the development of emphysema and pulmonary hypertension,” says Weißmann, who is the Chair of “Molecular Mechanisms of Emphysema, Hypoxia and Lung Aging” at JLU. There is an increased production of this enzyme during disease pathogenesis. Suppressing its production prevents the development of pulmonary emphysema und pulmonary hypertension in the model. “A similar regulation of NADPH oxidase also occurs in people with COPD,” he explains. “Our cellular studies in human tissue prove that identical biochemical processes occur in disease pathogenesis, so NoxO1 could be a new therapeutic target structure for the treatment of pulmonary emphysema.”
Weißmann, whose work group carried out the investigations in an international cooperation, heads the special research area 1213 “Pulmonary Hypertension and Pulmonary Heart Disease”. He is also a member of the steering committee of the CPI excellence cluster, a research association between JLU, Goethe University Frankfurt, and the Max Planck Institute for Heart and Lung Research in Bad Nauheim. It aims to develop concepts for the treatment of heart and lung diseases. The special research area, which also involves the Max Planck Institute and Campus Kerckhoff of Giessen University (JLU) as well as its Department of Medicine in Bad Nauheim and the Philipps University of Marburg, explores the pathogenetic mechanisms of pulmonary hypertension and right heart failure. The CPI and the special research area are funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).
Cigarette smoking and the increasing air pollution around the globe, especially in emerging industrial countries, are the major causes of chronic obstructive pulmonary disease (COPD), whose incidence is constantly increasing. WHO expects COPD to become the third leading cause of death in 2030.
In the final stage of the disease, the patients are physically severely limited, and their physical performance is significantly reduced. Little stress is already associated with shortness of breath and rapid exhaustion, so it is not uncommon that the patient needs temporary or permanent oxygen therapy. There is an increased production of mucus in the airways, and oxygen supply to the body is severely limited in end-stage COPD. Currently, progression cannot be stopped, and there is no cure for the disease. Therefore, current therapies rely on measures relieving the symptoms.
The clinical picture involves various manifestations: chronic bronchitis and pulmonary emphysema. In patients with chronic bronchitis, the larger airways are mainly affected, while in patients with pulmonary emphysema, there is a full destruction of the microstructure of the lungs, including dissolution of the alveoli and the small blood vessels of the lungs.
Prof. Dr. Norbert Weißmann
Spokesman of SFB 1213
Excellence cluster “The Cardio-Pulmonary Institute (CPI)”
Giessen University (JLU)
Phone: +49 641 99 42414
Seimetz, M., Sommer, N., Bednorz, M. et al.: NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD. Nature Metabolism (2020), DOI: 10.1038/s42255-020-0215-8