Trial reportAutophagy2014
Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.
Trial report in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Flavonoids in Nasal Therapeutics: Biological Activities, Delivery Challenges, and Formulation Strategies-A Systematic Review.Phytotherapy research : PTR · 2026Pooled it
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.PloS one · 2020Trial
- A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.Cell death and differentiation · 2016Trial
- Transglutaminase 2 regulates vimentin-dependent proteostasis during macrophage activation.Science advances · 2026Article
- Autophagy in the lung: guardian of homeostasis or driver of disease.Autophagy reports · 2025Review
- TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Understanding the molecular regulatory mechanisms of autophagy in lung disease pathogenesis.Frontiers in immunology · 2024Review
- Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5.Journal of medicinal chemistry · 2023Article
- Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.Molecules (Basel, Switzerland) · 2023Review
- The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.Frontiers in immunology · 2023Article
- Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing.International journal of molecular sciences · 2022Article
- The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases.Biomedicines · 2022Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry.Biomedicines · 2022Review
- Assays of CFTR Function In Vitro, Ex Vivo and In Vivo.International journal of molecular sciences · 2022Review
- How autophagy controls the intestinal epithelial barrier.Autophagy · 2022Review
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 13 institutions in 7 countries.
Funding
Abstract
Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.