Dornase-Alfa (DNase, Pulmozyme) for cystic fibrosis

MacConnachie, A.M.

doi:10.1016/s0964-3397(98)80268-1

Cited by 4 publications

(7 citation statements)

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“…One of the most common treatments is the inhalation of osmotic agents which, assuring an increase in mucociliary clearance [56], leads to better lung function within CF patients [57].…”

Section: Cystic Fibrosis: News On the Diseasementioning

confidence: 99%

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An Intriguing Involvement of Mitochondria in Cystic Fibrosis

Favia

Bari

Bobba

et al. 2019

JCM

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Cystic fibrosis (CF) occurs when the cystic fibrosis transmembrane conductance regulator (CFTR) protein is not synthetized and folded correctly. The CFTR protein helps to maintain the balance of salt and water on many body surfaces, such as the lung surface. When the protein is not working correctly, chloride becomes trapped in cells, then water cannot hydrate the cellular surface and the mucus covering the cells becomes thick and sticky. Furthermore, a defective CFTR appears to produce a redox imbalance in epithelial cells and extracellular fluids and to cause an abnormal generation of reactive oxygen species: as a consequence, oxidative stress has been implicated as a causative factor in the aetiology of the process. Moreover, massive evidences show that defective CFTR gives rise to extracellular GSH level decrease and elevated glucose concentrations in airway surface liquid (ASL), thus encouraging lung infection by pathogens in the CF advancement. Recent research in progress aims to rediscover a possible role of mitochondria in CF. Here the latest new and recent studies on mitochondrial bioenergetics are collected. Surprisingly, they have enabled us to ascertain that mitochondria have a leading role in opposing the high ASL glucose level as well as oxidative stress in CF.

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“…One of the most common treatments is the inhalation of osmotic agents which, assuring an increase in mucociliary clearance [56], leads to better lung function within CF patients [57].…”

Section: Cystic Fibrosis: News On the Diseasementioning

confidence: 99%

“…Another common treatment for CF patients is the inhalation of an enzyme deoxyribonuclease I that cleaves DNA in order to reduce the viscosity of the mucus [56,58]. Another treatment helping to slow the progression of CF disease is the chest physiotherapy [59].…”

Section: Cystic Fibrosis: News On the Diseasementioning

confidence: 99%

An Intriguing Involvement of Mitochondria in Cystic Fibrosis

Favia

Bari

Bobba

et al. 2019

JCM

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“…Drug repurposing is a key strategy to accelerate the discovery of new effective treatments for COVID-19 [ 18 ]. In this context, as the literature shows evidence of the role of NETs in COVID-19, DNase I, an FDA-approved drug that degrades NETs could be proposed as a potential new candidate for COVID-19 treatment [ 19 – 21 ]. Dornase alfa (recombinant human DNase I) is broadly used to improve lung function of patients with Cystic Fibrosis [ 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

et al. 2023

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Background COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. Methods Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers. Results DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. Conclusions Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.

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“…Coronavirus diseases 2019 (COVID- 19) is an infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1, 2) and pulmonaryrelated symptoms are one of its hallmarks (3,4). Neutrophils have been described as indicators of severity of respiratory symptoms and poor COVID-19 prognosis (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…Drug repurposing is a key strategy to accelerate discovery of new effective treatments for COVID-19 (18). In this context, as the literature shows evidence of the role of NETs in COVID-19, DNase I, an FDA-approved drug that degrades NETs could be proposed as a potential new candidate for COVID-19 treatment (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

Veras

Gomes

Silva

et al. 2022

Preprint

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COVID-19 is characterized by severe acute lung injury, which is associated with neutrophils infiltration and release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potential deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.

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Dornase-Alfa (DNase, Pulmozyme) for cystic fibrosis

Cited by 4 publications

References 0 publications

An Intriguing Involvement of Mitochondria in Cystic Fibrosis

An Intriguing Involvement of Mitochondria in Cystic Fibrosis

Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

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