Article
Respiratory System
Frederic Becq, Sandra Mirval, Thomas Carrez, Manuella Leveque, Arnaud Billet, Christelle Coraux, Edouard Sage, Anne Cantereau
Summary: Trikafta is currently the leading therapeutic in cystic fibrosis (CF) and has shown significant clinical benefits. This study compared the effects of different medications on F508del-CFTR cells and found that the combination therapy of elexacaftor/tezacaftor/ivacaftor effectively improved the abnormal expression and function of F508del-CFTR, but the presence of ivacaftor limited its efficacy. These findings suggest that the basal F508del-CFTR current may serve as a marker for correction efficacy in CF cells.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Kerstin Brinkert, Silke Hedtfeld, Annina Burhop, Rena Gastmeier, Pauline Gad, Dirk Wedekind, Christina Kloth, Justin Rothschuh, Nico Lachmann, Miriam Hetzel, Adan Chari Jirmo, Elena Lopez-Rodriguez, Christina Brandenberger, Gesine Hansen, Axel Schambach, Mania Ackermann, Burkhard Tuemmler, Antje Munder
Summary: This study found that hematopoietic stem cell transplantation to replace defective immune cells in cystic fibrosis mice resulted in improved survival and disease course in cases of airway infection. The successful engraftment of wild-type cells correlated with the better outcomes observed in infected mice.
Article
Biochemistry & Molecular Biology
Elodie Mareux, Martine Lapalus, Amel Ben Saad, Renaud Zelli, Mounia Lakli, Yosra Riahi, Marion Almes, Manon Banet, Isabelle Callebaut, Jean-Luc Decout, Thomas Falguieres, Emmanuel Jacquemin, Emmanuel Gonzales
Summary: The study investigated the mutations of the ABCB11 gene in PFIC2 patients and their functional rescue using specific drugs, providing new pharmacological approaches for treating ABCB11 deficiencies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Onofrio Laselva, Zafar Qureshi, Zhi-Wei Zeng, Evgeniy Petrotchenko, Mohabir Ramjeesingh, C. Michael Hamilton, Ling-Jun Huan, Christoph H. Borchers, Regis Pomes, Robert Young, Christine E. Bear
Summary: The study re-evaluated the binding of VX-770 to CFTR in biological membranes, suggesting that VX-770 may mediate potentiation through multiple sites in the CFTR protein.
Article
Chemistry, Multidisciplinary
Melissa Iazzi, Phillip Junor, Jitesh Doshi, Saujanya Acharya, Roxana Suhring, Russell D. Viirre, Gagan D. Gupta
Summary: Mutations in CFTR cause cystic fibrosis (CF), a fatal disease. Ivacaftor enhances CFTR channel activity and is approved for CF treatment. However, it may reduce the efficacy of combination therapy. Reducing the lipophilicity of ivacaftor can improve its efficacy for certain types of CFTR mutations.
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
Critical Care Medicine
Pierre-Regis Burgel, Isabelle Durieu, Raphael Chiron, Sophie Ramel, Isabelle Danner-Boucher, Anne Prevotat, Dominique Grenet, Christophe Marguet, Martine Reynaud-Gaubert, Julie Macey, Laurent Mely, Annlyse Fenton, Sebastien Quetant, Lydie Lemonnier, Jean-Louis Paillasseur, Jennifer Da Silva, Clemence Martin
Summary: An observational study in France found that the use of elexacaftor-tezacaftor-ivacaftor in CF patients led to significant improvements in lung function and weight within a short period of time, with most patients no longer requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding. Compared to the previous two years, there was a twofold decrease in the number of lung transplantations in CF patients in 2020.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Letter
Genetics & Heredity
Elodie Mareux, Martine Lapalus, Amel Ben-Saad, Isabelle Callebaut, Thomas Falguieres, Emmanuel Gonzales, Emmanuel Jacquemin
Summary: The study found that the ABCB11 p.A257V variant exhibits varying functional defects in different cells in vitro, and this defect can be fully rescued by Ivacaftor. This suggests that Ivacaftor may be an effective pharmacological tool for patients with ICP and PFIC2 caused by ABCB11 variations affecting ABCB11 function.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
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)
Article
Biochemistry & Molecular Biology
Carleen Mae Sabusap, Disha Joshi, Luba Simhaev, Kathryn E. Oliver, Hanoch Senderowitz, Marcel van Willigen, Ineke Braakman, Andras Rab, Eric J. Sorscher, Jeong S. Hong
Summary: Patients with cystic fibrosis carrying the P67L variant in CFTR often exhibit typical CF symptoms and show robust response to CFTR correctors. Biochemical measurements and molecular dynamics analysis suggest that the P67L mutation shares key pathogenic features with F508del and may impair the integrity of CFTR structure, providing a potential target for pharmacological repair.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Juliana Roda, Catarina Pinto-Silva, Iris A. I. Silva, Carla Maia, Susana Almeida, Ricardo Ferreira, Guiomar Oliveira
Summary: Cystic fibrosis is a chronic disease caused by mutations in the CFTR gene, affecting over 90,000 people worldwide. New drugs targeting the molecular defect of CFTR have the potential to provide personalized treatments for patients with cystic fibrosis.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2022)
Article
Immunology
Hanna Schmidt, Larissa Melina Hoepfer, Lisa Wohlgemuth, Christiane Leonie Knapp, Adam Omar Khalaf Mohamed, Laura Stukan, Frederik Muennich, Dominik Huesken, Alexander Sebastian Koller, Alexander Elias Paul Stratmann, Paul Mueller, Christian Karl Braun, Dorit Fabricius, Sebastian Felix Nepomuk Bode, Markus Huber-Lang, David Alexander Christian Messerer
Summary: Cystic fibrosis is a monogenetic disease caused by CFTR impairment. ETI treatment has shown positive effects on patients, reducing sweat chloride levels and improving pulmonary function, but has no significant impact on cellular innate immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, General & Internal
Jamie Duckers, Beth Lesher, Teja Thorat, Eleanor Lucas, Lisa J. McGarry, Keval Chandarana, Fosca De Iorio
Summary: Real-world studies show that ivacaftor treatment in people with cystic fibrosis results in highly consistent and sustained clinical benefit in both pulmonary and non-pulmonary outcomes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Young Jin Kim, Tomoki Nomakuchi, Foteini Papaleonidopoulou, Lucia Yang, Qian Zhang, Adrian R. Krainer
Summary: An antisense oligonucleotide cocktail has been developed to restore CFTR protein function by gene-specific stabilization of CFTR mRNA and increase the expression of CFTR-W1282X mRNA, providing a potential therapy for cystic fibrosis caused by the W1282X mutation. The treatment has been shown to enhance CFTR-mediated chloride current in human bronchial epithelial cells.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Karen S. Raraigh, Kathleen C. Paul, Jennifer L. Goralski, Erin N. Worthington, Anna Faino, Stanley Sciortino, Yiting Wang, Melis A. Aksit, Hua Ling, Derek L. Osorio, Frankline M. Onchiri, Shivani U. Patel, Christian A. Merlo, Kristina Montemayor, Ronald L. Gibson, Natalie E. West, Amita Thakerar, Robert J. Bridges, David N. Sheppard, Neeraj Sharma, Garry R. Cutting
Summary: The presence of specific CFTR variants can cause dysfunction in chloride channels, which is generally associated with the severity of cystic fibrosis. However, some individuals with these variants do not consistently display overt cystic fibrosis features. A study found that a certain variant, F312del, occurs at a higher-than-expected frequency in the general population, suggesting that individuals with this variant and a CF-causing variant may not develop typical cystic fibrosis features. This finding provides additional insight into the molecular understanding of the response to ivacaftor.
Editorial Material
Gastroenterology & Hepatology
Chantal Housset
CURRENT OPINION IN GASTROENTEROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Amel Ben Saad, Alix Bruneau, Elodie Mareux, Martine Lapalus, Jean-Louis Delaunay, Emmanuel Gonzales, Emmanuel Jacquemin, Tounsia Ait-Slimane, Thomas Falguieres
Summary: ABC transporters expressed at the canalicular membrane of hepatocytes are crucial for bile secretion by secreting bile acids, phosphatidylcholine, cholesterol, drugs, and other compounds. Dysfunctions in these transporters lead to rare, severe biliary diseases, emphasizing the importance of studying their biology for developing new therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Amel Ben Saad, Virginie Vauthier, Agota Toth, Angelika Janaszkiewicz, Anne-Marie Durand-Schneider, Alix Bruneau, Jean-Louis Delaunay, Martine Lapalus, Elodie Mareux, Isabelle Garcin, Emmanuel Gonzales, Chantal Housset, Tounsia Ait-Slimane, Emmanuel Jacquemin, Florent Di Meo, Thomas Falguieres
Summary: Certain CFTR correctors can rescue the maturation and canalicular localization of ABCB4 variants, but do not restore their secretion activity and also inhibit the activity of wild type ABCB4. In silico molecular docking analyses suggest direct interaction of these correctors with the transporter's transmembrane domains and ATP-binding sites.
LIVER INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Amel Ben Saad, Virginie Vauthier, Martine Lapalus, Elodie Mareux, Evangeline Bennana, Anne-Marie Durand-Schneider, Alix Bruneau, Jean-Louis Delaunay, Emmanuel Gonzales, Chantal Housset, Tounsia Ait-Slimane, Francois Guillonneau, Emmanuel Jacquemin, Thomas Falguieres
Summary: ABCB4 is an ABC transporter crucial for phosphatidylcholine secretion into bile. Research has identified RAB10 as a novel molecular partner of ABCB4, influencing its plasma membrane expression and function. Understanding the interactions between RAB10 and ABCB4 may lead to the development of novel therapies for liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Charlotte Bouzbib, Haquima El Mourabit, Dominique Wendum, Elisabeth Lasnier, Sarah Mouri, Chantal Housset, Dominique Thabut, Nicolas Weiss, Marika Rudler
Summary: The pathophysiology of acute encephalopathy in cirrhotic patients is not fully understood. Recent studies have indicated increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy. This study focused on the modification of ATP-binding cassette (ABC) transporters in the BBB and found a possible association between the expression of MRP5 and drug-induced acute encephalopathy in cirrhosis.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Augustin Schaefer, Martin Journaux, Haquima El Mourabit, Sarah Mouri, Dominique Wendum, Elisabeth Lasnier, Pierre-Olivier Couraud, Chantal Housset, Dominique Thabut, Marika Rudler, Nicolas Weiss
Summary: The study found that the plasma of cirrhotic patients with HE enhances leukocyte TEM across the hCMEC/D3 BBB model. There was a correlation between U937 TEM, West-Haven score, and ammonemia. A trend towards a correlation between U937 TEM and PS-100Beta in plasma, a marker of increased BBB permeability, was also observed.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Svetlana Varyukhina, Antonin Lamaziere, Jean Louis Delaunay, Anaelle de Wreede, Jesus Ayala-Sanmartin
Summary: The research demonstrated that Annexin A2 has the ability to modulate membrane lipid rearrangement by altering cholesterol distribution and lipid compactness, resulting in changes in membrane order in cellular regions.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Review
Gastroenterology & Hepatology
Alix Bruneau, Adrien Guillot, Frank Tacke
Summary: Cholangiopathies are a heterogeneous class of liver diseases where cholangiocytes are the main targets of liver injury. Available therapies mainly target bile acids and related signaling pathways, but the mechanisms underlying inflammation, ductular reaction, and fibrosis are still poorly understood.
CURRENT OPINION IN GASTROENTEROLOGY
(2022)
Article
Cell Biology
Alix Bruneau, Jean-Louis Delaunay, Anne-Marie Durand-Schneider, Virginie Vauthier, Amel Ben Saad, Lynda Aoudjehane, Haquima El Mourabit, Romain Morichon, Thomas Falguieres, Jeremie Gautheron, Chantal Housset, Tounsia Ait-Slimane
Summary: This study identifies MRCK alpha and MRLC as novel partners of ABCB4, and shows that they regulate the cell surface expression of ABCB4.
Article
Gastroenterology & Hepatology
Lin Lei, Alix Bruneau, Haquima El Mourabit, Justine Guegan, Trine Folseraas, Sara Lemoinne, Tom Hemming Karlsen, Benedicte Hoareau, Romain Morichon, Ester Gonzalez-Sanchez, Claire Goumard, Vlad Ratziu, Pierre Charbord, Jeremie Gautheron, Frank Tacke, Thierry Jaffredo, Axelle Cadoret, Chantal Housset
Summary: This study identified portal mesenchymal progenitors of myofibroblasts in liver fibrosis and revealed their role in myofibroblast formation. Portal mesenchymal progenitors play a crucial role in the formation of fibrotic septa, along with neovessels and HSC-MFs that arise from a preexisting pool.
Article
Multidisciplinary Sciences
Julie Magusto, Carine Beaupere, Marta B. Afonso, Martine Auclair, Jean-Louis Delaunay, Pierre-Antoine Soret, Gilles Courtois, Tounsia Ait-Slimane, Chantal Housset, Isabelle Jeru, Bruno Feve, Vlad Ratziu, Cecilia M. P. Rodrigues, Jeremie Gautheron
Summary: RIPK3 and MLKL have distinct roles in adipocyte differentiation, with MLKL deficiency blocking white adipocyte differentiation but not beige adipocyte differentiation, highlighting the therapeutic potential of MLKL inhibition in obesity.
Article
Biochemistry & Molecular Biology
Jean-Louis Delaunay, Ahmad Elbahnsi, Alix Bruneau, Claire Madry, Anne-Marie Durand-Schneider, Anne Stary, Chantal Housset, Jeremie Gautheron, Isabelle Callebaut, Tounsia Ait-Slimane
Summary: ABCB4 is a hepatocanalicular floppase that plays a role in biliary phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene can cause biliary diseases, including PFIC3. This study demonstrates that ten missense variations in ABCB4 can be rescued by the CFTR potentiator ivacaftor, indicating a potential treatment option for PFIC3 patients with ATP-binding site mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)