Trial reportCell death and differentiation2016
A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.
Trial report in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
What it found
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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
54 citing papers in PubMed, 91 citations in OpenAlex.
- Understanding the molecular regulatory mechanisms of autophagy in lung disease pathogenesis.Frontiers in immunology · 2024Review
- Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases.International journal of molecular sciences · 2023Review
- Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.Molecules (Basel, Switzerland) · 2023Review
- Cytoplasmic YAP1-mediated ESCRT-III assembly promotes autophagic cell death and is ubiquitinated by NEDD4L in breast cancer.Cancer communications (London, England) · 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
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 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
- Assays of CFTR Function In Vitro, Ex Vivo and In Vivo.International journal of molecular sciences · 2022Review
- Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis.Respiratory medicine · 2022Article
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- Autophagy in major human diseases.The EMBO journal · 2021Review
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- A SNARE protein Syntaxin 17 captures CFTR to potentiate autophagosomal clearance under stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Cystic Fibrosis Lung Disease in the Aging Population.Frontiers in pharmacology · 2021Review
- Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.Frontiers in immunology · 2021Review
- Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation.International journal of molecular sciences · 2020Review
- Metabolomics profiling of tobacco exposure in children with cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
- Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis.Science advances · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.
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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.