Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Article
Pediatrics
Qiyu Li, Siyuan Liu, Xuemei Ma, Jiaping Yu
Summary: This meta-analysis evaluated the effectiveness and safety of small molecule therapy in children diagnosed with cystic fibrosis (CF). The results showed that CFTR modulators can improve respiratory function, lung clearance index, sweat chloride concentration, and other aspects of function in children with CF, with comparable adverse events compared to the placebo group.
FRONTIERS IN PEDIATRICS
(2022)
Review
Pharmacology & Pharmacy
Yizi Wang, Bin Ma, Wenya Li, Peiwen Li
Summary: Triple combination therapy for cystic fibrosis patients achieves better clinical results and comparable adverse events compared to the control group.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Michael D. Kim, Charles D. Bengtson, Makoto Yoshida, Asef J. Niloy, John S. Dennis, Nathalie Baumlin, Matthias Salathe
Summary: Highly effective modulator therapies greatly improve prognosis for cystic fibrosis patients. However, not all patients with the most common F508del mutation in CFTR benefit from ETI therapy. The study found that elevated levels of active TGF-??1 in the upper airway were associated with poor response to ETI, as evidenced by low sweat chloride concentrations and lack of lung function improvements. TGF-??1 impaired the function of corrected F508del-CFTR and led to increased absorption rates of airway surface liquid and mucus hyperconcentration in vitro. Losartan reversed the negative effects of TGF-??1 and improved ASL hydration in CF airway epithelium.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Chemistry, Medicinal
Marc J. C. Scanio, Xenia B. Searle, Bo Liu, John R. Koenig, Robert J. Altenbach, Gregory A. Gfesser, Andrew Bogdan, Stephen Greszler, Gang Zhao, Ashvani Singh, Yihong Fan, Andrew M. Swensen, Timothy Vortherms, Arlene Manelli, Corina Balut, Wenqing Gao, Hong Yong, Michael Schrimpf, Chris Tse, Philip Kym, Xueqing Wang
Summary: Cystic fibrosis (CF) is a disease caused by mutations in both copies of the CFTR gene, with the most common mutation being the deletion of phenylalanine at position 508 of the CFTR protein. The most effective treatment for CF currently involves using a combination of CFTR correctors and potentiators. This study focuses on the identification and exploration of the structure-activity relationship of C2 correctors for CFTR, to be used in conjunction with existing C1 correctors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, General & Internal
Lotte Vanherle, Darcy Lidington, Franziska E. Uhl, Saskia Steiner, Stefania Vassallo, Cecilia Skoug, Joao M. N. Duarte, Sangeetha Ramu, Lena Uller, Jean-Francois Desjardins, Kim A. Connelly, Steffen-Sebastian Bolz, Anja Meissner
Summary: Our study investigated the mechanisms that alter hippocampal neurons following myocardial infarction (MI) and explored the therapeutic potential of correcting cystic fibrosis transmembrane regulator (CFTR) as an intervention. We found that MI leads to reduced hippocampal dendrite length and spine density, which is associated with decreased neuronal CFTR expression and inflammatory responses. Blocking CFTR activity down-regulates synaptic regulator PSD-95 expression in neurons, while pharmacologically correcting CFTR expression rescues the down-regulation. Increasing hippocampal neuron CFTR expression improves MI-associated alterations in neuronal structure and memory function. These findings suggest that CFTR therapeutics can attenuate cognitive impairment in heart failure patients.
Article
Gastroenterology & Hepatology
Zhi-Wei Dong, Hui Liu, Fei-Fei Su, Xiao-Zhou Fan, Yong Zhang, Peng Liu
Summary: CFTR overexpression inhibits hypoxia/reoxygenation-induced apoptosis through the PI3K/AKT/NF-kappa B signaling pathway in Caco2 cells and intestinal tissues.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Laura Carrasco-Hernandez, Esther Quintana-Gallego, Carmen Calero, Rocio Reinoso-Arija, Borja Ruiz-Duque, Jose Luis Lopez-Campos
Summary: The role of CFTR in the pathophysiology of COPD is becoming increasingly important, with its dysfunction leading to thicker and more viscous secretions in the airway, reduced mucociliary clearance, and promotion of airway inflammation. Studying CFTR in the context of COPD pathogenesis is crucial for a comprehensive understanding of COPD's complex pathophysiology and exploring potential therapeutic approaches to address this dysfunction.
Article
Biochemistry & Molecular Biology
Ho K. Lee, Jinhong Park, Bo-Rahm Kim, Ikhyun Jun, Tae-im Kim, Wan Namkung
Summary: The study identified isorhamnetin as a novel CFTR activator for treating dry eye disease, which increased tear volume and reduced ocular surface damage and inflammatory cytokine expression in an experimental mouse model of dry eye. The findings suggest that isorhamnetin could be a potential therapeutic agent for dry eye disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chiara Brandas, Alessandra Ludovico, Alice Parodi, Oscar Moran, Enrico Millo, Elena Cichero, Debora Baroni
Summary: Cystic fibrosis is caused by loss-of-function mutations in the CFTR protein, with F508del being the most common mutation. Small molecules called correctors have been developed to rescue defective F508del CFTR, showing better results when used in combinations. Targeting different structural and functional defects of mutant CFTR with corrector combinations appears to be the most promising therapeutic approach for a larger cohort of CF patients.
Article
Biochemistry & Molecular Biology
Kavisha Arora, Pramodha Liyanage, Qing Zhong, Anjaparavanda P. Naren
Summary: The study reveals that under nutritional stress and bacterial infection, the autophagic SNARE protein syntaxin17 (Stx17) interacts with CFTR to facilitate efficient lysosomal clearance, playing a critical role in preventing defective autophagy.
Article
Respiratory System
Rebecca J. Birch, Daniel Peckham, Henry M. Wood, Philip Quirke, Rob Konstant-Hambling, Keith Brownlee, Rebecca Cosgriff, Nicholas Burr, Amy Downing
Summary: It has been found that individuals with Cystic Fibrosis (CF) have a higher risk of developing colorectal cancer (CRC), and carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations may also face an increased risk. With the increasing life expectancy of CF patients, more individuals are at risk of developing CRC.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Immunology
Franziska E. Uhl, Lotte Vanherle, Anja Meissner
Summary: Heart failure (HF) affects 64 million people worldwide. Pulmonary manifestations of HF, including lung inflammation and vascular structure changes, contribute to the poor quality of life for many HF patients. This study investigates the role of cystic fibrosis transmembrane regulator (CFTR) in lung inflammation during HF and suggests that pharmacological correction of CFTR expression could alleviate HF-associated lung inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sangam Rajak, Archana Tewari, Sana Raza, Pratima Gupta, Bandana Chakravarti, Baby Anjum, Madhulika Tripathi, Brijesh K. Singh, Paul M. Yen, Amit Goel, Sujoy Ghosh, Rohit A. Sinha
Summary: Nonalcoholic steatohepatitis (NASH) is a pivotal stage in the progression of nonalcoholic fatty liver disease (NAFLD) and increases the risk of serious liver diseases. Identifying reliable molecular players in the etiology of NASH has been difficult. Furthermore, there are currently no approved drugs for NASH treatment. This study highlights the involvement of CFTR in the pathogenesis of NASH and suggests the possibility of its pharmacological inhibition in human NASH.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
