Article
Multidisciplinary Sciences
Martin Y. Ng, Hong Li, Mikel D. Ghelfi, Yale E. Goldman, Barry S. Cooperman
Summary: This study investigates the effects of ataluren and G418 on read-through, finding that ataluren exclusively stimulates read-through by inhibiting release factor activity, while G418 increases near-cognate tRNA mispairing with a PSC. The low toxicity of ataluren suggests that developing new TRIDs aimed at inhibiting termination should be a priority in combating PSC diseases. Additionally, the research provides rate measurements of certain steps during the eukaryotic translation elongation cycle, showing how these rates are altered when cognate tRNA is replaced by near-cognate tRNA +/- TRIDs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Sara H. Osum, Eunice I. Oribamise, Stanislas M. A. S. Corbiere, Mandy Taisto, Tyler Jubenville, Alex Coutts, Mark N. Kirstein, James Fisher, Christopher Moertel, Ming Du, David Bedwell, David A. Largaespada, Adrienne L. Watson
Summary: Neurofibromatosis type 1 (NF1) is caused by germline mutations in the tumor-suppressor gene NF1, leading to an increased risk of nervous system tumors. In this study, a minipig model of NF1 carrying a premature termination codon (PTC) was used to investigate the potential of nonsense suppression in restoring expression of the NF1-encoded protein neurofibromin. The results showed that nonsense suppression did not significantly increase neurofibromin in primary NF1-'- Schwann cells, but it reduced phosphorylated ERK.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Dermatology
Jiangfan Yu, Bingsi Tang, Xinglan He, Puyu Zou, Zhuotong Zeng, Rong Xiao
Summary: This article summarizes the current research status of nonsense suppression therapy for hereditary skin diseases and discusses the potential opportunities and challenges of applying new technologies related to nonsense suppression therapy to dermatology. Further research is needed to explore the potential of nonsense suppression therapy as a safer and more specific treatment strategy for hereditary skin diseases.
ACTA DERMATO-VENEREOLOGICA
(2022)
Article
Respiratory System
E. de Poel, S. Spelier, S. W. F. Suen, E. Kruisselbrink, S. Y. Graeber, M. A. Mall, E. J. M. Weersink, M. M. van der Eerden, G. H. Koppelman, C. K. van der Ent, J. M. Beekman
Summary: This study assessed the effect of drugs targeting translational readthrough (RT), nonsense mRNA mediated decay (NMD), and CFTR protein modulation on CFTR function in intestinal organoids of people with cystic fibrosis. The results showed that a quintuple combination of drugs can effectively rescue PTC CFTR protein function, reaching clinical relevance.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Medicine, Research & Experimental
Ryoko Semba, Takamitsu Morioka, Hiromi Yanagihara, Kenshi Suzuki, Hirotaka Tachibana, Takahiro Hamoya, Yoshiya Horimoto, Tatsuhiko Imaoka, Mitsue Saito, Shizuko Kakinuma, Masami Arai
Summary: This study found that the macrolide antibiotic azithromycin has inhibitory effects on intestinal tumorigenesis in mice with a nonsense mutation in the Apc gene. It suppresses tumor growth and adenocarcinoma formation, while also restoring the levels of full-length Apc protein and downregulating β-catenin and cyclin D1. However, the impact of azithromycin on the diversity of intestinal microbiota depends on the concentration used.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Daniel R. McHugh, Calvin U. Cotton, Craig A. Hodges
Summary: This study demonstrated synergy between NMD inhibitors and readthrough agents in increasing functional protein quantity following readthrough, suggesting a potential therapeutic option for treating nonsense mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Adi Amar-Schwartz, Yuval Cohen, Antony Elhaj, Vered Ben-Hur, Zahava Siegfried, Rotem Karni, Talya Dor
Summary: Duchene muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are genetic neuromuscular disorders caused by mutations in the dystrophin gene, and read-through therapies combined with NMD inhibitors may improve the treatment outcomes for these diseases by increasing the levels of mutant dystrophin mRNA.
HUMAN MOLECULAR GENETICS
(2023)
Article
Respiratory System
Daniel K. Crawford, Jasper Mullenders, Johanna Pott, Sylvia F. Boj, Shira Landskroner-Eiger, Matthew M. Goddeeris
Summary: ELX-02 promotes read-through of mRNA transcripts with nonsense mutations in CF patient-derived organoids, leading to increased CFTR activity and expression. These findings support the potential of ELX-02 as a read-through agent for CF caused by the G542X allele.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Review
Biochemistry & Molecular Biology
Sacha Spelier, Eveline P. M. van Doorn, Cornelis K. van der Ent, Jeffrey M. Beekman, Martijn A. J. Koppens
Summary: Approximately 10% of pathological mutations are nonsense mutations causing severe genetic disorders without effective treatments. Ribosomal readthrough is the common strategy to treat nonsense mutations and restore full-length protein production. Despite promising preclinical results on readthrough compounds, clinical studies have not shown positive outcomes. We review both preclinical and clinical research on readthrough compounds and discuss factors contributing to the translational gap.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Health Care Sciences & Services
Xiubin Liang, Mohamad Bouhamdan, Xia Hou, Kezhong Zhang, Jun Song, Ke Hao, Jian-Ping Jin, Zhongyang Zhang, Jie Xu
Summary: The study identified a new CF animal model that exhibits intestinal dysbiosis phenotype, which may facilitate research and development of novel treatments for CF-associated gastrointestinal diseases. The fecal microbiomes of CF rabbits showed lower richness and diversity compared to wild-type rabbits, indicating significant taxonomic and functional dysbiosis.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Cell Biology
Joao F. Ferreira, Iris A. L. Silva, Hugo M. Botelho, Margarida D. Amaral, Carlos M. Farinha
Summary: This research uncovers the role of EPAC1 in stabilizing PM CFTR levels in intestinal cells, providing a potential target for the development of novel combinatorial therapies for the treatment of CF.
Article
Respiratory System
Eva Furstova, Tereza Dousova, Jakub Beranek, Malgorzata Libik, Libor Fila, Martin Modrak, Ondrej Cinek, Milan Macek, Pavel Drevinek
Summary: This study compared the in vitro responses of two CFTR modulator drug combinations and explored potential inter-individual variability in therapeutic response to the triple combination. The findings showed that elexacaftor/tezacaftor/ivacaftor was more effective than tezacaftor/ivacaftor in cystic fibrosis patients with a specific genotype. The presence of unique CFTR variants in one sample suggests that genetic traits beyond the CF-causing CFTR mutation may influence the response to modulator drugs.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Respiratory System
Anabela S. Ramalho, Eva Fuerstova, Annelotte M. Vonk, Marc Ferrante, Catherine Verfaillie, Lieven Dupont, Mieke Boon, Marijke Proesmans, Jeffrey M. Beekman, Ifat Sarouk, Carlos Vazquez Cordero, Francois Vermeulen, Kris De Boeck
Summary: In patients with CF, CFTR function in intestinal organoids correlates closely with sweat chloride values, and the rescue of CFTR function by CFTR modulators in organoids is tightly associated with improvements in lung function and sweat chloride levels reported in clinical trials. Candidate genotypes for modulator therapy have been identified based on organoid results, suggesting that organoids may serve as a potential in vitro model to guide precision medicine for patients with rare CFTR mutations.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Medicine, Research & Experimental
Wooree Ko, Joseph J. Porter, Matthew T. Sipple, Katherine M. Edwards, John D. Lueck
Summary: This study establishes the ACE-tRNA approach as a potential standalone therapeutic for nonsense-associated diseases, as it is able to rescue both mRNA and full-length protein expression from PTC-containing endogenous genes.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Lisa W. Rodenburg, Livia Delpiano, Violeta Railean, Raquel Centeio, Madalena C. Pinto, Shannon M. A. Smits, Isabelle S. van der Windt, Casper F. J. van Hugten, Sam F. B. van Beuningen, Remco N. P. Rodenburg, Cornelis K. van der Ent, Margarida D. Amaral, Karl Kunzelmann, Michael A. Gray, Jeffrey M. Beekman, Gimano D. Amatngalim
Summary: This study identified 12 FDA-approved drugs that can induce CFTR-independent fluid secretion through a medium-throughput screening of nasal CF airway epithelial organoids. The findings provide a new perspective for the treatment of CF patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Respiratory System
Michael A. Lensink, Sarah N. Boers, Karin R. Jongsma, Sarah E. Carter, Cornelis K. van der Ent, Annelien L. Bredenoord
Summary: The study highlights the ethical challenges of organoid biobanking in CF precision medicine, including issues related to commercial involvement, informed consent procedures, and the blurring boundary between research and clinical care. Professionals suggest finding a balanced approach in governance to address these challenges effectively.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Pediatrics
Sabine E. van der Laan, Marieke L. A. de Hoog, Sanne L. Nijhof, Ulrike Gehring, Judith M. Vonk, Cornelis K. van der Ent, Alet H. Wijga
Summary: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive good or excellent general health.
JOURNAL OF PEDIATRICS
(2021)
Article
Allergy
Hannah M. Kansen, Francine C. van Erp, Andre C. Knulst, Anna M. Ehlers, Sarah A. Lyons, Edward F. Knol, Yolanda Meijer, Henny G. Otten, Cornelis K. van der Ent, Thuy-My Le
Summary: The diagnostic value of peanut components in adults with suspected peanut allergy was evaluated, with sIgE to Ara h 2 and Ara h 6 identified as the best predictors. A cutoff level of 1.75 kUA/L for Ara h 2 was validated to accurately predict peanut allergy in one-third of adult patients.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Health Care Sciences & Services
Maartje I. Kristensen, Karin M. de Winter-de Groot, Gitte Berkers, Mei Ling J. N. Chu, Kayleigh Arp, Sophie Ghijsen, Harry G. M. Heijerman, Hubertus G. M. Arets, Christof J. Majoor, Hettie M. Janssens, Renske van der Meer, Debby Bogaert, Cornelis K. van der Ent
Summary: In this study, it was found that Ivacaftor treatment significantly increased bacterial diversity and overall microbiota composition in the gut of CF patients carrying one S1251N mutation. However, there were no significant changes in the overall microbial composition and alpha diversity in the upper and lower airways of these patients after Ivacaftor treatment.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Martin van Eijk, Albert van Dijk, Cornelis K. van Der Ent, Hubertus G. M. Arets, Eefjan Breukink, Nico van Os, Roy Adrichem, Sven van Der Water, Rita Lino Gomez, Maartje Kristensen, Martin Hessing, Shehrazade Jekhmane, Markus Weingarth, Ruud A. W. Veldhuizen, Edwin J. A. Veldhuizen, Henk P. Haagsman
Summary: PepBiotics, a novel class of antimicrobial peptides, showed promising antibacterial properties against CF-related respiratory pathogens, with CR-163 demonstrating the most potential for treatment. These observations highlight the therapeutic potential of PepBiotics against CF-related bacterial respiratory infections.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Letter
Education, Scientific Disciplines
Stefan van Geelen, Merel Dekker, Kors van der Ent
Article
Pediatrics
Emma E. Berkelbach van der Sprenkel, Sanne L. Nijhof, Geertje W. Dalmeijer, N. Charlotte Onland-Moret, Simone A. de Roos, Heidi M. B. Lesscher, Elise M. van de Putte, Cornelis K. van der Ent, Catrin Finkenauer, Gonneke W. J. M. Stevens
Summary: This study examined the psychosocial functioning of adolescents with chronic diseases and their family members, using data from the Dutch 2013 HBSC survey. Findings suggest that chronically diseased adolescents experience impaired psychosocial functioning across various life domains, and healthy adolescents with chronically diseased family members also show significant differences in psychosocial outcomes. Additionally, healthy adolescents with chronically diseased family members reported more positive outcomes compared to those adolescents who had a chronic disease themselves.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Respiratory System
Danya Muilwijk, Eyleen De Poel, Peter Van Mourik, Sylvia W. F. Suen, Annelotte M. Vonk, Jesse E. Brunsveld, Evelien Kruisselbrink, Hugo Oppelaar, Marne C. Hagemeijer, Gitte Berkers, Karin M. De Winter-De Groot, Sabine Heida-Michel, Stephan R. Jans, Hannah Van Panhuis, Menno M. Van der Eerden, Renske Van der Meer, Jolt Roukema, Edward Dompeling, Els J. M. Weersink, Gerard H. Koppelman, Robert Vries, Domenique D. Zomer-Van Ommen, Marinus J. C. Eijkemans, Cornelis K. Van der Ent, Jeffrey M. Beekman
Summary: This study examines the association of forskolin-induced swelling (FIS) of patient-derived organoids with long-term cystic fibrosis (CF) disease progression. The results show that FIS is strongly associated with changes in lung function and the development of CF-related complications, such as pancreatic insufficiency, liver disease, and diabetes.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Respiratory System
E. de Poel, S. Spelier, S. W. F. Suen, E. Kruisselbrink, S. Y. Graeber, M. A. Mall, E. J. M. Weersink, M. M. van der Eerden, G. H. Koppelman, C. K. van der Ent, J. M. Beekman
Summary: This study assessed the effect of drugs targeting translational readthrough (RT), nonsense mRNA mediated decay (NMD), and CFTR protein modulation on CFTR function in intestinal organoids of people with cystic fibrosis. The results showed that a quintuple combination of drugs can effectively rescue PTC CFTR protein function, reaching clinical relevance.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Health Care Sciences & Services
Danya Muilwijk, Marlou Bierlaagh, Peter van Mourik, Jasmijn Kraaijkamp, Renske van der Meer, Rutger van den Bor, Harry Heijerman, Rene Eijkemans, Jeffrey Beekman, Kors van der Ent
Summary: A multicenter observational cohort study found that certain biomarkers may be used to predict clinical outcomes of patients with cystic fibrosis receiving LUM/IVA treatment.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Respiratory System
Jacquelien J. Noordhoek, Joshena Jeyaratnam, Domenique Zomer, Vincent A. M. Gulmans, Cornelis K. van der Ent, Harry G. M. Heijerman
Summary: The Dutch CF Foundation (NCFS) developed a quality improvement program to assess and improve the quality of care in CF centers in the Netherlands. Patient assessments, online surveys, and site visits were used to evaluate quality of care and provide recommendations, mainly focused on communication issues. All centers received the quality mark from the patient organization, with the majority implementing the recommendations after two years, demonstrating the program's high efficacy.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Respiratory System
Domenique Zomer, Jakko van Ingen, Regina Hofland, Dutch C. F. Registry Steering group Dutch CF Registry Steering Grp
Summary: A survey and retrospective data analysis from the Dutch CF Registry were conducted to assess the epidemiology and management of NTM isolation and disease in pwCF in the Netherlands. The study revealed an increasing prevalence of NTM isolation, poor treatment outcomes, and an association with declining lung function. The prevention and treatment of NTM pulmonary disease among pwCF in the Netherlands require increased attention.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Medicine, General & Internal
Danya Muilwijk, Tessa J. van Paridon, Doris C. van der Heijden, Brenda M. Faber-Bisschop, Domenique D. Zomer-van Ommen, Harry G. M. Heijerman, Cornelis K. van der Ent
Summary: This study developed and validated a novel personalized electronic patient-reported outcome measure (PROM) that accurately captures relevant aspects of quality of life in individuals with Cystic Fibrosis. The tool demonstrated strong internal consistency and test-retest reliability, and was associated with existing assessment tools and physiological indicators. The findings suggest that this personalized ePROM is a reliable, valid, and sensitive measure of quality of life for individuals with Cystic Fibrosis.
Article
Respiratory System
Danya Muilwijk, Domenique D. Zomer-Van Ommen, Vincent A. M. Gulmans, Marinus J. C. Eijkemans, Cornelis K. Van der Ent
Summary: This registry-based cohort study evaluated the long-term effectiveness of dual cystic fibrosis transmembrane conductance regulator (CFTR) modulators in real-world settings and found that the improvement in forced expiratory volume, body mass index, and antibiotic treatment duration was less pronounced than in clinical trials and varied considerably among patients with different baseline lung function.
Article
Pediatrics
Merel M. Nap-van der Vlist, Geertje W. Dalmeijer, Martha A. Grootenhuis, Kors van der Ent, Marry M. Van den Heuvel-Eibrink, Joost F. Swart, Elise M. van de Putte, Sanne L. Nijhof
Summary: Fatigue among children with a chronic disease is multidimensional. Various generic biological/lifestyle, psychological, and social factors are strongly associated with fatigue, explaining 58.4%, 65.8%, and 50.0% of the variance in fatigue, respectively. Overall, almost three-quarters of the variance in fatigue can be explained by this biopsychosocial model.
BMJ PAEDIATRICS OPEN
(2021)
