ArticleHuman molecular genetics2019
HDAC inhibitors rescue multiple disease-causing CFTR variants.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Review
- Transcriptomic and functional responses of the cystic fibrosis airway epithelium to CFTR modulator therapy.JCI insight · 2025Article
- Molecular Mediators of Neutrophil Primary Granule Release Following Acute Ischemic Stroke and their Associated Epigenetic Modulation by HDAC2.Molecular neurobiology · 2025Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- Deacetylation of Histones and Non-histone Proteins in Inflammatory Diseases and Cancer Therapeutic Potential of Histone Deacetylase Inhibitors.Current genomics · 2023Review
- Triangulating variation in the population to define mechanisms for precision management of genetic disease.Structure (London, England : 1993) · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants.Molecular biology of the cell · 2022Article
- Downregulation of epithelial sodium channel (ENaC) activity in cystic fibrosis cells by epigenetic targeting.Cellular and molecular life sciences : CMLS · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- Beyond Mendelian Inheritance: Genetic Buffering and Phenotype Variability.Phenomics (Cham, Switzerland) · 2022Review
- Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology.Journal of medicinal chemistry · 2022Review
- Dual Blockade of Misfolded Alpha-Sarcoglycan Degradation by Bortezomib and Givinostat Combination.Frontiers in pharmacology · 2022Article
- Role of Histone Post-Translational Modifications in Inflammatory Diseases.Frontiers in immunology · 2022Review
- Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts.ACS pharmacology & translational science · 2021Article
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Small Molecules Restore Bestrophin 1 Expression and Function of Both Dominant and Recessive Bestrophinopathies in Patient-Derived Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2020Article
- Phenotyping of RareCells · 2020Article
- Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.Nature communications · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding the role of the epigenome in protein-misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable response of the disease population to therapeutics. An ever-growing body of evidence has shown that histone deacetylase (HDAC) inhibitors (HDACi) can have significant benefit in correcting protein-misfolding diseases that occur in response to both familial and somatic mutation. Cystic fibrosis (CF) is a familial autosomal recessive disease, caused by genetic diversity in the CF transmembrane conductance regulator (CFTR) gene, a cyclic Adenosine MonoPhosphate (cAMP)-dependent chloride channel expressed at the apical plasma membrane of epithelial cells in multiple tissues. The potential utility of HDACi in correcting the phenylalanine 508 deletion (F508del) CFTR variant as well as the over 2000 CF-associated variants remains controversial. To address this concern, we examined the impact of US Food and Drug Administration-approved HDACi on the trafficking and function of a panel of CFTR variants. Our data reveal that panobinostat (LBH-589) and romidepsin (FK-228) provide functional correction of Class II and III CFTR variants, restoring cell surface chloride channel activity in primary human bronchial epithelial cells. We further demonstrate a synergistic effect of these HDACi with Vx809, which can significantly restore channel activity for multiple CFTR variants. These data suggest that HDACi can serve to level the cellular playing field for correcting CF-causing mutations, a leveling effect that might also extend to other protein-misfolding diseases.
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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.