scholarly journals Not as easy as it looks: Gene therapy for cystic fibrosis

2008 ◽  
Vol 30 (3) ◽  
pp. 22-25
Author(s):  
Tim Lee ◽  
Eric Blair
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Respiratory Tract ◽  
Low Levels

The gene responsible for cystic fibrosis (CF) was first identified in 1989. Since that time, gene therapy has held the promise of a cure for cystic fibrosis; however, progress has been much slower than initially hoped. Clinical trials of gene therapy have demonstrated that the corrected CF gene can be expressed successfully in the respiratory tract of subjects with CF, but only for approximately 30 days at best, and at low levels.

scholarly journals Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 218 ◽  
Author(s):  
Laura Marquez Loza ◽  
Eric Yuen ◽  
Paul McCray
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Insertional Mutagenesis ◽  
Primary Cultures ◽  
Severe Combined Immunodeficiency ◽  
Lentiviral Vectors ◽  
Retroviral Vectors ◽  
Airway Epithelia

Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as those with nonsense mutations, CFTR gene transfer to airway epithelia offers the potential for an effective treatment. Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Studies in primary cultures of human CF airway epithelia and CF animal models demonstrate the long-term correction of CF phenotypes and low immunogenicity using lentiviral vectors. Further development of CF gene therapy requires the investigation of optimal CFTR expression in the airways. Lentiviral vectors with improved safety features have minimized insertional mutagenesis safety concerns raised in early clinical trials for severe combined immunodeficiency using γ-retroviral vectors. Recent clinical trials using improved lentiviral vectors support the feasibility and safety of lentiviral gene therapy for monogenetic diseases. While work remains to be done before CF gene therapy reaches the bedside, recent advances in lentiviral vector development reviewed here are encouraging and suggest it could be tested in clinical studies in the near future.

For the treatment of cystic fibrosis, RNA medicines, gene transfer therapies, and gene editing treatments have potential

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Acid Treatment ◽  
Gene Editing ◽  
Healthy Adult ◽  
Phase 1 ◽  
Clinical Settings ◽  
Potential Harm ◽  
Cohesive Group

Many unique genetic procedures have been created to reach the heart of the cystic fibrosis (CF) problem, overcoming a defective gene, and advances in the nucleic acid treatment industry have made these methods much more viable as potential remedies. However, before any of these approaches can be used in clinical settings, a number of hurdles must be overcome, including determining which organs should be targeted for the most robust effect with the least amount of potential harm; determining which cells should be targeted in each organ; and determining what constitutes a successful treatment. Another factor to consider is that, unlike many other treatments, gene therapy and gene editing will need advancing clinical trials ahead without data from healthy adult control cohorts; rather, phase 1 studies will require CF patients. Furthermore, we must select which patients should be included in the initial studies for mutation-agnostic methods: should we include all patients, even if effective modulator therapy is available? Clearly, if we are to be successful, we will have to face some significant challenges, and we will have to do it as a cohesive group, as we have always done.

scholarly journals Innovative therapies in genetic diseases: Cystic fibrosis

2021 ◽  
Vol 70 (1) ◽  
pp. 16-20
Author(s):  
Elena-Silvia Shelby ◽  
◽  
Florina Mihaela Nedelea ◽  
Tanser Huseyinoglu ◽  
Relu Cocos ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Antisense Oligonucleotides ◽  
Viral Vectors ◽  
Genetic Diseases ◽  
Wild Type ◽  
Gene Encoding ◽  
Innovative Therapies ◽  
Type Gene

Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.

Respiratory tract microbiocenosis in children with cystic fibrosis in Kharkiv region

2016 ◽  
Vol 78 (6) ◽  
pp. 24-26
Author(s):  
V.A. Klymenko ◽  
◽  
Y.A. Yanovskaya ◽  
Y.V. Pasichnik ◽  
◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract

Towards More Successful Gene Therapy Clinical Trials for β-Thalassemia

2013 ◽  
Vol 13 (8) ◽  
pp. 1314-1330 ◽  
Author(s):  
E. Drakopoulou ◽  
E. Papanikolaou ◽  
M. Georgomanoli ◽  
N. Anagnou
Keyword(s):  
Gene Therapy ◽  
Clinical Trials

Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Mononuclear Cells ◽  
Multiple Organ ◽  
Peripheral Blood Mononuclear ◽  
Dornase Alfa ◽  
Tract Infections ◽  
Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

scholarly journals Variation in treatment preferences of pulmonary exacerbations among Australian and New Zealand cystic fibrosis physicians

2021 ◽  
Vol 8 (1) ◽  
pp. e000956
Author(s):  
Grace Currie ◽  
Anna Tai ◽  
Tom Snelling ◽  
André Schultz
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Trials ◽  
New Zealand ◽  
Treatment Options ◽  
Early Response ◽  
Treatment Preferences ◽  
Dornase Alfa ◽  
Clinical Scenarios ◽  
Professional Opinion ◽  
Pulmonary Exacerbations

BackgroundDespite advances in cystic fibrosis (CF) management and survival, the optimal treatment of pulmonary exacerbations remains unclear. Understanding the variability in treatment approaches among physicians might help prioritise clinical uncertainties to address through clinical trials.MethodsPhysicians from Australia and New Zealand who care for people with CF were invited to participate in a web survey of treatment preferences for CF pulmonary exacerbations. Six typical clinical scenarios were presented; three to paediatric and another three to adult physicians. For each scenario, physicians were asked to choose treatment options and provide reasons for their choices.ResultsForty-nine CF physicians (31 paediatric and 18 adult medicine) participated; more than half reported 10+ years of experience. There was considerable variation in primary antibiotic selection; none was preferred by more than half of respondents in any scenario. For secondary antibiotic therapy, respondents consistently preferred intravenous tobramycin and a third antibiotic was rarely prescribed, except in one scenario describing an adult patient. Hypertonic saline nebulisation and twice daily chest physiotherapy was preferred in most scenarios while dornase alfa use was more variable. Most CF physicians (>80%) preferred to change therapy if there was no early response. Professional opinion was the most common reason for antibiotic choice.ConclusionsVariation exists among CF physicians in their preferred choice of primary antibiotic and use of dornase alfa. These preferences are driven by professional opinion, possibly reflecting a lack of evidence to base policy recommendations. Evidence from high-quality clinical trials is needed to inform physician decision making.

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