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
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.
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
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
Reproductive Biology
Leo Han, Mackenzie Roberts, Addie Luo, Shuhao Wei, Ov D. Slayden, Kelvin D. Macdonald
Summary: This study demonstrates the hormonal regulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression in endocervical cells, both in vitro and in vivo. The researchers also showed that endocervical epithelial cells can be conditionally reprogrammed to study CFTR ion channel function. Furthermore, the study found that estrogen upregulates CFTR expression in the macaque cervix, which is blocked by cotreatment with progesterone.
BIOLOGY OF REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Philip R. Tedbury, Candela Manfredi, Frauke Degenhardt, Joseph Conway, Michael C. Horwath, Courtney McCracken, Adam J. Sorscher, Sandy Moreau, Christine Wright, Carolina Edwards, Jo Brewer, Jeannette Guarner, Emmie de Wit, Brandi N. Williamson, Mehul S. Suthar, Yee T. Ong, John D. Roback, David N. Alter, Jan C. Holter, Tom H. Karlsen, Nicoletta Sacchi, Manuel Romero-Gomez, Pietro Invernizzi, Javier Fernandez, Maria Buti, Agustin Albillos, Antonio Julia, Luca Valenti, Rosanna Asselta, Jesus M. Banales, Luis Bujanda, Rafael de Cid, Andre Franke, Stefan G. Sarafianos, Jeong S. Hong, Eric J. Sorscher, Annette Ehrhardt
Summary: Patients with cystic fibrosis (CF) are not highly susceptible to severe COVID-19 despite initial concerns. CFTR carrier status does not affect the severity of COVID-19 clinical outcomes. However, mortality rates are higher in control individuals compared to silent carriers of the common F508del CFTR variant, which requires further investigation. The acidic, viscous, and mucus-obstructed airways in CF patients are unfavorable for coronavirus infection.
Article
Biochemistry & Molecular Biology
Philip R. Tedbury, Candela Manfredi, Frauke Degenhardt, Joseph Conway, Michael C. Horwath, Courtney McCracken, Adam J. Sorscher, Sandy Moreau, Christine Wright, Carolina Edwards, Jo Brewer, Jeannette Guarner, Emmie de Wit, Brandi N. Williamson, Mehul S. Suthar, Yee T. Ong, John D. Roback, David N. Alter, Jan C. Holter, Tom H. Karlsen, Nicoletta Sacchi, Manuel Romero-Gomez, Pietro Invernizzi, Javier Fernandez, Maria Buti, Agustin Albillos, Antonio Julia, Luca Valenti, Rosanna Asselta, Jesus M. Banales, Luis Bujanda, Rafael de Cid, Andre Franke, Stefan G. Sarafianos, Jeong S. Hong, Eric J. Sorscher, Annette Ehrhardt
Summary: Patients with cystic fibrosis (CF) do not have a higher risk of severe COVID-19 due to CFTR carrier status, but control individuals have a higher mortality rate compared to silent carriers. The absence of functional CFTR does not affect the production of SARS-CoV-2 in airway cells, while in vitro experiments suggest that virus proliferation is dependent on features disrupted by absent CFTR in patients with CF. The acidic, viscous, and mucus-obstructed airways in CF patients are unfavorable for coronaviral infection establishment.
Article
Multidisciplinary Sciences
Melanie Faria da Cunha, Iwona Pranke, Ali Sassi, Christiane Schreiweis, Stephanie Moriceau, Dragana Vidovic, Aurelie Hatton, Mariane Sylvia Carlon, Geordie Creste, Farouk Berhal, Guillaume Prestat, Romain Freund, Norbert Odolczyk, Jean Philippe Jais, Christine Gravier-Pelletier, Piotr Zielenkiewicz, Vincent Jullien, Alexandre Hinzpeter, Franck Oury, Aleksander Edelman, Isabelle Sermet-Gaudelus
Summary: This study provides the first in vivo preclinical evidence of the efficacy of c407 in treating Cystic Fibrosis, correcting CFTR dysfunction and improving chloride conductance. Importantly, c407 was well tolerated and demonstrated no obvious toxicity after systemic administration.
SCIENTIFIC REPORTS
(2022)
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
Medicine, Research & Experimental
Yanqiu Wang, Hui Wei, Yazhong Ji, Feiping Liu, Zhijun Shen, Xunyi Zhang
Summary: The study evaluated the levels of CFTR in infertile females of different age groups and found significant differences in indicators of oocyte quality and general features among them, indicating an association between CFTR and female age.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Elizabeth Marie Gavioli, Nerli Guardado, Farah Haniff, Nouran Deiab, Etty Vider
Summary: Treatment with CFTR modulators has improved clinical outcomes and increased lifespans of CF patients. However, there are safety concerns, such as elevations in liver enzymes and drug-drug interactions, associated with these drugs. postmarketing studies are needed to determine long-term safety concerns.
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
(2021)
Article
Nutrition & Dietetics
Susannah J. King, Audrey C. Tierney, Deirdre Edgeworth, Dominic Keating, Elyssa Williams, Tom Kotsimbos, Brenda M. Button, John W. Wilson
Summary: Ivacaftor treatment led to initial gains in fat-free mass in the first month, with weight, BMI, and fat mass increases plateauing within the first 6 months and remaining stable over 2.5 years. The long-term metabolic and clinical implications of weight and fat mass gains are still unknown.
Article
Multidisciplinary Sciences
Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, Marco Cipolli
Summary: As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. However, current clinical evidence suggests that cystic fibrosis may actually protect against SARS-CoV-2 infection. The expression of SARS-CoV-2 receptors in primary airway epithelial cells is regulated by the CFTR channel, and dysfunctional CFTR channels in cystic fibrosis cells result in reduced viral entry and replication.
NATURE COMMUNICATIONS
(2023)
Review
Medicine, Research & Experimental
Shijing Jia, Jennifer L. Taylor-Cousar
Summary: Cystic fibrosis (CF) is a genetic disease that affects multiple organ systems and can lead to various complications. Traditional treatments focused on managing the symptoms of each affected system. However, the development of modulator therapies targeted at specific genetic mutations has significantly improved the lives and prognosis of CF patients.
ANNUAL REVIEW OF MEDICINE
(2023)