GENE THERAPY CLINICAL TRIALS FOR CYSTIC FIBROSIS: VIRAL AND NON-VIRAL APPROACHES

1999 ◽  
pp. 244-267
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Clinical Trials

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.

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

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.

scholarly journals DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 441
Author(s):  
Fanny Pineau ◽  
Davide Caimmi ◽  
Sylvie Taviaux ◽  
Maurane Reveil ◽  
Laura Brosseau ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dna Methylation ◽  
Clinical Trials ◽  
Lung Disease ◽  
Disease Severity ◽  
Genome Wide ◽  
A Genome ◽  
Lung Disease Severity ◽  
Epigenetic Biomarker

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

scholarly journals The United States’ Regulatory Environment Is Evolving to Accommodate a Coming Boom in Gene Therapy Research

2019 ◽  
Vol 24 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Daniel Eisenman
Keyword(s):  
United States ◽  
Gene Therapy ◽  
Clinical Trials ◽  
The United States ◽  
Regulatory Environment ◽  
Evidence Based ◽  
Regulatory Structure ◽  
Regulatory Changes ◽  
Current State ◽  
Therapy Field

Introduction: A dramatic increase in the number of clinical trials involving gene-modified cell therapy and gene therapy is taking place. The field is on the verge of a boom, and the regulatory environment is evolving to accommodate the growth. Discussion: This commentary summarizes the current state of the field, including an overview of the growth. The United States (US) regulatory structure for gene therapy will be summarized, and the evolution of the oversight structure will be explained. Conclusion: The gene therapy field has recently produced its first FDA-approved therapeutics and has a pipeline of other investigational products in the final stages of clinical trials before they can be evaluated by the FDA as safe and effective therapeutics. As research continues to evolve, so must the oversight structure. Biosafety professionals and IBCs have always played key roles in contributing to the safe, evidence-based advancement of gene therapy research. With the recent regulatory changes and current surge in gene therapy research, the importance of those roles has increased dramatically.

Sign in / Sign up

Export Citation Format

Share Document