PEGylation of Recombinant Human Deoxyribonuclease I Provides a Long‐Acting Version of the Mucolytic for Patients with Cystic Fibrosis

2020 ◽  
pp. 2000146 ◽  
Author(s):  
Marie‐Julie Guichard ◽  
Tobias Wilms ◽  
Sohaib Mahri ◽  
Harshad P. Patil ◽  
Delphine Hoton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Deoxyribonuclease I ◽  
Long Acting

scholarly journals Impact of PEGylation on the mucolytic activity of recombinant human deoxyribonuclease I in cystic fibrosis sputum

2018 ◽  
Vol 132 (13) ◽  
pp. 1439-1452 ◽  
Author(s):  
Marie-Julie Guichard ◽  
David Kinoo ◽  
Anne-Sophie Aubriot ◽  
Nathalie Bauwens ◽  
Jordane Gougué ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Weight ◽  
Polyethylene Glycol ◽  
Enzymatic Activity ◽  
Macroscopic Appearance ◽  
Cystic Fibrosis Sputum ◽  
Deoxyribonuclease I ◽  
Rapid Clearance ◽  
The Stability ◽  
Long Acting

Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs and reduce its administration frequency. Here, we evaluated the enzymatic activity of rhDNase conjugated to a two-arm 40 kDa polyethylene glycol (PEG40) in CF sputa. Rheology data indicated that both rhDNase and PEG40-rhDNase presented similar mucolytic activity in CF sputa, independently of the purulence of the sputum samples as well as of their DNA, actin and ions contents. The macroscopic appearance of the samples correlated with the DNA content of the sputa: the more purulent the sample, the higher the DNA concentration. Finally, quantification of the enzymes in CF sputa following rheology measurement suggests that PEGylation largely increases the stability of rhDNase in CF respiratory secretions, since 24-fold more PEG40-rhDNase than rhDNase was recovered from the samples. The present results are considered positive and provide support to the continuation of the research on a long acting version of rhDNase to treat CF lung disease.

Use of rhDNase Therapy and Costs of Respiratory-Related Care in Patients with Cystic Fibrosis

2000 ◽  
Vol 34 (3) ◽  
pp. 304-308 ◽  
Author(s):  
Daniel A Ollendorf ◽  
Lisa J McGarry ◽  
Marc L Watrous ◽  
Gerry Oster
Keyword(s):  
Cystic Fibrosis ◽  
New England ◽  
Median Number ◽  
Deoxyribonuclease I ◽  
Outpatient Physician ◽  
Level Of Use ◽  
The Us ◽  
The Relationship ◽  
Health Hospital

OBJECTIVE: To assess the relationship between level of use of recombinant deoxyribonuclease I (rhDNase) therapy and costs of respiratory-related care in patients with cystic fibrosis. DESIGN: Retrospective, cohort study using healthcare claims data from a large New England health insurer. PATIENTS: All cystic fibrosis patients five years of age and older who began therapy with rhDNase in 1994 (the year it was first marketed in the US). Healthcare claims were compiled for six months prior to first receipt of rhDNase (pretreatment) and for 30 months subsequently (follow-up). Patients were stratified according to their level of rhDNase use during follow-up, based on whether it was above or below the median number of therapy days for the sample. MAIN OUTCOME MEASURES: Costs of rhDNase, all antibiotics, and all respiratory-related outpatient (physician, home health, hospital outpatient) and inpatient care were included. All costs were expressed on an annualized basis. RESULTS: Twenty-four patients with cystic fibrosis who began treatment with rhDNase in 1994 met all entry criteria; the median number of therapy days over a 30-month period was 355. Among patients with low (i.e., below the median) rhDNase use (n = 12), mean ± SD annualized costs of respiratory-related care increased by almost $17000 between pretreatment and follow-up, from $29251 ± $37919 to $46109 ± $40944. Among high-use patients (n = 12), costs decreased by approximately $2500, from $37178 ± $48476 to $34592 ± $22591. The change in both groups was accounted for primarily by a change in the number of respiratory-related hospitalizations. CONCLUSIONS: Prolonged use of rhDNase may reduce costs of respiratory-related care in patients with cystic fibrosis; further study is required, however, to confirm these findings.

P227 A long-acting alternative DNase for the treatment of cystic fibrosis lung disease

2020 ◽  
Vol 19 ◽  
pp. S120-S121
Author(s):  
G. Mori ◽  
D. Delfino ◽  
A. Grigoletto ◽  
G. Bizzotto ◽  
G. Pasut ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Cystic Fibrosis Lung ◽  
Cystic Fibrosis Lung Disease ◽  
Long Acting

A Preliminary Study of Aerosolized Recombinant Human Deoxyribonuclease I in the Treatment of Cystic Fibrosis

1992 ◽  
Vol 326 (12) ◽  
pp. 812-815 ◽  
Author(s):  
Richard C. Hubbard ◽  
Noel G. McElvaney ◽  
Peter Birrer ◽  
Steven Shak ◽  
Woodrow W. Robinson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Deoxyribonuclease I ◽  
Preliminary Study

Production and characterization of a PEGylated derivative of recombinant human deoxyribonuclease I for cystic fibrosis therapy

2017 ◽  
Vol 524 (1-2) ◽  
pp. 159-167 ◽  
Author(s):  
Marie-Julie Guichard ◽  
Harshad P. Patil ◽  
Salome Juliette Koussoroplis ◽  
Ruddy Wattiez ◽  
Teresinha Leal ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Deoxyribonuclease I

scholarly journals The novel long acting ENaC blocker P643 has therapeutic effects in chronic cystic fibrosis-like lung disease in mice

2009 ◽  
Vol 8 ◽  
pp. S26
Author(s):  
Z. Zhou ◽  
M. Harm ◽  
D.A. Treis ◽  
S.C. Schubert ◽  
J. Schatterny ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Therapeutic Effects ◽  
The Novel ◽  
Long Acting

Cystic fibrosis: a diagnosis in an adolescent

2021 ◽  
Vol 14 (11) ◽  
pp. e245971
Author(s):  
Monica Bennett ◽  
Andreia Filipa Nogueira ◽  
Maria Manuel Flores ◽  
Teresa Reis Silva
Keyword(s):  
Cystic Fibrosis ◽  
Inhaled Corticosteroids ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Sweat Test ◽  
Oral Antibiotic ◽  
Atypical Symptoms ◽  
Oral Antibiotic Therapy ◽  
Long Acting ◽  
First Year Of Life

Most patients with cystic fibrosis (CF) develop multisystemic clinical manifestations, the minority having mild or atypical symptoms. We describe an adolescent with chronic cough and purulent rhinorrhoea since the first year of life, with diagnoses of asthma, allergic rhinitis and chronic rhinosinusitis. Under therapy with long-acting bronchodilators, antihistamines, inhaled corticosteroids, antileukotrienes and several courses of empirical oral antibiotic therapy, there was no clinical improvement. There was no reference to gastrointestinal symptoms. Due to clinical worsening, extended investigations were initiated, which revealed Pseudomonas aeruginosa in sputum culture, sweat test with a positive result and heterozygosity for F508del and R334W mutations in genetic study which allowed to confirm the diagnosis of CF. In this case, heterozygosity with a class IV mutation can explain the atypical clinical presentation. It is very important to consider this diagnosis when chronic symptoms persist, despite optimised therapy for other respiratory pathologies and in case of isolation of atypical bacterial agents.

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