Article
Pharmacology & Pharmacy
Nicole Reyne, Patricia Cmielewski, Alexandra McCarron, Juliette Delhove, David Parsons, Martin Donnelley
Summary: The study evaluated the effect of lentiviral-mediated CFTR airway gene delivery on nasal PD in a CFTR knockout rat model, showing that the gene therapy resulted in a mean correction of 46% towards wild-type chloride response in treated CF rats.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Charles Bengtson, Neerupma Silswal, Nathalie Baumlin, Makoto Yoshida, John Dennis, Sireesha Yerrathota, Michael Kim, Matthias Salathe
Summary: This study explored the effects of the CFTR amplifier nesolicaftor on CFTR function and ciliary beating in an inflammatory environment, demonstrating that nesolicaftor can enhance the response of F508del CFTR to the modulator ETI, and reverse the effects of TGF-beta 1 on CFTR function and cytokine expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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.
Review
Biochemistry & Molecular Biology
Caitlyn Harvey, Sinead Weldon, Stuart Elborn, Damian G. Downey, Clifford Taggart
Summary: The advent of CFTR modulators in cystic fibrosis treatment has transformed the management of the disease, shifting it from being a life-limiting condition to one that can be effectively managed. These genotype-specific therapies have shown significant improvements in various clinical endpoints, but their effects on pathogenic burden and airway infection need further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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, General & Internal
Hannah Farley, Sarah Poole, Stephen Chapman, William Flight
Summary: A retrospective single-center cohort study identified 19 adult patients diagnosed with CF, all of whom had a history of chronic respiratory symptoms and the majority of whom had a CFTR genotype considered eligible for CFTR modulator therapy.
POSTGRADUATE MEDICAL JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Oscar Fonseca, Maria Salome Gomes, Maria Adelina Amorim, Ana Cordeiro Gomes
Summary: Cystic fibrosis, a monogenic disease, has a diverse clinical presentation involving chronic lung infection, inflammation, and reduced bone mass. The underlying mechanisms of reduced bone mass in cystic fibrosis patients are still unclear. This review explores the relationship between CFTR dysfunction and intrinsic bone defects, as well as the impact of the proinflammatory environment and chronic infection on bone mass maintenance in CF patients.
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)
Article
Pharmacology & Pharmacy
L. Clara Mok, Antonio Garcia-Uceda, Matthew N. Cooper, Mariette Kemner Van De Corput, Marleen De Bruijne, Nathalie Feyaerts, Tim Rosenow, Kris De Boeck, Stephen Stick, Harm A. W. M. Tiddens
Summary: Newly developed quantitative CT outcomes designed for CF lung disease can assess structural abnormalities. CFTR modulators have the potential to reduce these abnormalities. This study aimed to investigate the effect of CFTR modulators on the progression of structural lung disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Francesca Saluzzo, Luca Riberi, Barbara Messore, Nicola Ivan Lore, Irene Esposito, Elisabetta Bignamini, Virginia De Rose
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to imbalances in the airway microenvironment and increased susceptibility to infections. CFTR modulators have shown promise in improving airway infections, but their long-term effects remain to be fully understood.
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
Gastroenterology & Hepatology
Nancy M. Walker, Jinghua Liu, Sarah M. Young, Rowena A. Woode, Lane L. Clarke
Summary: Studies on small intestinal organoids from cystic fibrosis (CF) mice show that goblet cell hyperplasia and increased Toll-like receptor 2/4 expression are not primary manifestations of the CF intestine. Goblet cell hyperplasia in CF mice can be induced by a Tlr2-dependent suppression of Notch signaling in both wild-type and CF intestinal organoids.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Aniello Meoli, Olaf Eickmeier, Giovanna Pisi, Valentina Fainardi, Stefan Zielen, Susanna Esposito
Summary: Cystic fibrosis, a genetically inherited disease caused by mutations in the CFTR gene, is a life-threatening disorder affecting multiple systems. CFTR modulators play a crucial role in influencing and eventually restoring lung phagocyte function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Margarete Olivier, Alexandra Kavvalou, Matthias Welsner, Raphael Hirtz, Svenja Strassburg, Sivagurunathan Sutharsan, Florian Stehling, Mathis Steindor
Summary: A retrospective analysis was conducted to evaluate the effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis. The results showed significant improvements in pulmonary function and nutritional status after 3 and 6 months of treatment. The therapy was found to be safe, although dose reductions and temporary interruptions were necessary in some cases.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Lucile Regard, Clemence Martin, Esperie Burnet, Jennifer Da Silva, Pierre-Regis Burgel
Summary: Cystic fibrosis is a rare genetic multisystemic disease caused by mutations in the CFTR gene, and CFTR modulators have shown clinical efficacy in restoring CFTR protein function. However, questions remain regarding their long-term safety and effectiveness, especially in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. Further research is needed to investigate the impact of CFTR modulators on important outcomes such as concurrent treatments, lung transplantation, chest imaging, and pregnancies.
Article
Respiratory System
Isobel E. R. MacKenzie, Valerie Paquette, Frances Gosse, Sheenagh George, Frederic Chappe, Valerie Chappe
JOURNAL OF CYSTIC FIBROSIS
(2017)
Article
Medicine, Research & Experimental
Maral Aali, Alexa Caldwell, Kelsey House, Juan Zhou, Valerie Chappe, Christian Lehmann
MEDICAL HYPOTHESES
(2017)
Review
Pharmacology & Pharmacy
Diogo R. Poroca, Ryan M. Pelis, Valerie M. Chappe
FRONTIERS IN PHARMACOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Kyungsoo Shin, Michael Landsman, Stephanie Pelletier, Bader N. Alamri, Younes Anini, Jan K. Rainey
Review
Pharmacology & Pharmacy
Anna Semaniakou, Roger P. Croll, Valerie Chappe
FRONTIERS IN PHARMACOLOGY
(2019)
Article
Nutrition & Dietetics
Brandon J. Gheller, Mary Gheller, Athena Li, Fernando Nunes, Younes Anini, N. Theresa Glanville, Nick Bellissimo, Jill Hamilton, G. Harvey Anderson, Bohdan L. Luhovyy
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2019)
Article
Critical Care Medicine
Marilyn Macdonald, Ariella Lang, Eileen Savage, Valerie Chappe, Andrea Murphy, Frances Gosse, Heather MacLean
Article
Nutrition & Dietetics
Kathleen Mather, Ruth Boachie, Younes Anini, Shirin Panahi, G. Harvey Anderson, Bohdan L. Luhovyy
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2020)
Article
Respiratory System
Anna Semaniakou, Sarah Brothers, Grayson Gould, Mehrsa Zahiremani, Jamie Paton, Frederic Chappe, Audrey Li, Younes Anini, Roger P. Croll, Valerie Chappe
Summary: Vasoactive Intestinal Peptide (VIP) is a major physiological agonist of CFTR chloride channel activity, functioning as a vasodilator, bronchodilator, and regulator of exocrine gland secretions. Reduction of VIP in CF tissues may represent an early aggravating factor for cystic fibrosis progression.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Multidisciplinary Sciences
Lara Ribeiro-Parenti, Anne-Charlotte Jarry, Jean-Baptiste Cavin, Alexandra Willemetz, Johanne Le Beyec, Aurelie Sannier, Samira Benadda, Anne-Laure Pelletier, Muriel Hourseau, Thibaut Leger, Bastien Morlet, Anne Couvelard, Younes Anini, Simon Msika, Jean-Pierre Marmuse, Severine Ledoux, Maude Le Gall, Andre Bado
Summary: This study reveals the presence of GLP-1 expressing cells in the stomach, which secrete active GLP-1 and are influenced by weight loss surgeries. Gastric glucose load induces a rapid increase in GLP-1 levels, and obese rats and individuals who undergo surgery exhibit changes in gastric mucosa phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Behavioral Sciences
William H. Gendron, Emre Fertan, Stephanie Pelletier, Kyle M. Roddick, Timothy P. O'Leary, Younes Anini, Richard E. Brown
Summary: In addition to cognitive decline, patients with Alzheimer's disease may exhibit sensory, motor, and neuropsychiatric deficits, as well as weight loss. The 5xFAD mouse model has been found to show age-related weight loss compared to wildtype controls, suggesting potential metabolic dysfunction.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Christian Lehmann, Nazli Alizadeh-Tabrizi, Stefan Hall, Sufyan Faridi, Irene Euodia, Bruce Holbein, Juan Zhou, Valerie Chappe
Summary: The iron chelator, DIBI, exhibits beneficial anti-inflammatory effects in experimental acute lung injury by reducing histopathological damage, inflammatory mediator levels, and NF-kappa B p65 activation.
Review
Biochemistry & Molecular Biology
Bader N. Alamri, Kyungsoo Shin, Valerie Chappe, Younes Anini
HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION
(2016)