Related Experiment Videos
New treatment strategies in cystic fibrosis: rhDNase
1Dept of Cystic Fibrosis, Royal Brompton Hospital, London, UK.
Insights
Recombinant human deoxyribonuclease (rhDNase) effectively treats cystic fibrosis (CF) lung disease by reducing sputum DNA. Clinical studies show rhDNase improves lung function and reduces exacerbations in CF patients.
Area of Science:
- Pulmonary Medicine
- Genetics
- Pharmacology
Background:
- Cystic fibrosis (CF) is a common inherited disease causing significant pulmonary morbidity and mortality.
- High sputum deoxyribonucleic acid (DNA) content contributes to the viscoelasticity of CF sputum.
- Recombinant human deoxyribonuclease I (rhDNase) is developed to target DNA in CF sputum.
Purpose of the Study:
- To review in vivo clinical studies evaluating the safety and efficacy of rhDNase for pulmonary disease in CF patients.
- To assess the benefits of rhDNase in conjunction with conventional CF therapies.
Main Methods:
- Review of Phase I, II, and III clinical trials assessing rhDNase safety and efficacy.
- Analysis of data from studies involving intermittent administration, severely ill patients, and different delivery systems.
- Longer-term open-label studies were also reviewed.
Main Results:
- Phase II studies indicated improvements in pulmonary function and a favorable safety profile.
- Phase III study demonstrated significant improvements in forced expiratory volume in one second (FEV1) with once and twice daily rhDNase treatment.
- rhDNase treatment reduced the risk of pulmonary exacerbations and showed some improvement in quality of life.
Conclusions:
- Recombinant human deoxyribonuclease is a safe and effective new therapy for pulmonary disease in cystic fibrosis.
- rhDNase provides clinical benefits for CF patients when used alongside conventional treatments.
Abstract:
Cystic fibrosis (CF) is the commonest inherited disease of the Caucasian population, with a high morbidity and mortality from pulmonary disease. The high viscoelasticity of CF sputum is due, in part, to the high deoxyribonucleic acid (DNA) content. Recombinant human deoxyribonuclease I (rhDNase) has been developed and in vitro studies have shown that it reduces the viscoelasticity of CF sputum. This article reviews the in vivo clinical studies conducted to determine the safety and efficacy of rhDNase in the treatment of pulmonary disease in CF. Initial Phase I studies showed preliminary safety and some evidence of clinical benefit. Subsequently, two Phase II studies were conducted in the US and UK during which patients received rhDNase for 10 days. A Phase III study of 24 weeks duration involving 968 patients in 51 centres in North America is also reported in detail. Longer term open-label studies, the results of intermittent administration, administration to severely ill patients and the use of different delivery systems are reviewed. The Phase II study reported improvements in pulmonary function and had a good safety profile. The Phase III study showed improvement in forced expiratory volume in one second (FEV1) of 5.8 and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation was reduced by 28% with once daily treatment and 37% with twice daily treatment compared to placebo. The drug was safe and there was some improvement in quality of life data. Recombinant human deoxyribonuclease is a new therapy for pulmonary disease in cystic fibrosis which has been shown to benefit patients when used in conjunction with conventional therapy.