Emily’s Entourage supported the research that resulted in the following publications.
JOURNAL OF CYSTIC FIBROSIS
September 2025
Intra-individual diversity of bacteriophage susceptibility in Burkholderia cultured from cystic fibrosis sputum
AUTHORS
Ortal Yerushalmy, Abby M. Korn, Guichan Yao, Carlos F. Gonzalez, Jason J. Gill, Linda M. Kalikin, Theodore Spilker, Lindsay J. Cavelry, Amy A. Mumford, Nathan R. Wallace, Saima Aslam, Ran Nir-Paz, Daria Van Tyne, John J. LiPuma
SUMMARY
Bacteriophage (phage) therapy is being explored to treat airway infections in people with cystic fibrosis (CF), but bacterial diversity during chronic infection may complicate treatment. In this study, Burkholderia isolates from CF sputum samples showed mixed sensitivity and resistance to phages, with 75% of samples containing both phage-sensitive and phage-resistant bacteria. These findings highlight the need to account for bacterial heterogeneity when developing phage therapies for CF.
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MOLECULAR DIAGNOSIS & THERAPY
September 2025
Personalized medicine in cystic fibrosis: Characterization of eight rare CFTR variants in intestinal organoids and cellular models
AUTHORS
Violeta Railean, Cláudia S. Rodrigues, Ines Pankonien, Sofia S. Ramalho, Iris A. L. Silva, Tereza Doušová, Susana Castanhinha, Pilar Azevedo, Juliana Roda, Carlos M. Farinha, Margarida D. Amaral
SUMMARY
This study evaluated eight rare CFTR variants to determine whether currently approved CFTR modulator (CFTRm) drugs could restore their function. Using patient-derived intestinal organoids and CF bronchial epithelial cells, the researchers found that most variants were rescued by CFTRm therapy, and patients who received treatment showed improved lung function and reduced sweat chloride levels. These results demonstrate that organoid-based assays can effectively predict clinical response to CFTR modulators for people with rare CFTR mutations.
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FRONTIERS IN PHARMACOLOGY
August 2025
CFTR ion transport deficiency primes the epithelium for partial epithelial-mesenchymal transition in cystic fibrosis
AUTHORS
Cláudia S. Rodrigues, Matilde Canto, Raquel Torres, Violeta Railean, Sofia S. Ramalho, Carlos M. Farinha, Ines Pankonien, Margarida D. Amaral
SUMMARY
Cystic fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a Cl−/HCO3− ion channel located at the apical plasma membrane (PM) of epithelial cells. CFTR dysfunction disrupts epithelial barrier integrity, drives progressive airway remodelling and has been associated with epithelial-to-mesenchymal transition (EMT), a process in which cells lose epithelial properties and acquire mesenchymal characteristics. We previously demonstrated that mutant CFTR directly drives partial EMT, independently of secondary events such as bacterial infection or inflammation.
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NUCLEIC ACIDS RESEARCH
July 2025
ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis
AUTHORS
Wooree Ko, Joseph J. Porter, Sacha Spelier, Emily G. Sorensen, Priyanka Bhatt, Jeffery T. Gabell, Isabelle van der Windt, Tyler Couch, Kevin Coote, Martin Mense, Jeffrey M. Beekman, John D. Lueck
SUMMARY
This study demonstrates that anticodon-edited tRNAs can efficiently suppress the most common cystic fibrosis–causing nonsense mutations, restoring CFTR transcript abundance and channel function across multiple patient-derived models, highlighting their potential as a therapeutic platform for CF and other nonsense-associated diseases.
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JOURNAL OF CYSTIC FIBROSIS
May 2025
Personalized therapy with CFTR modulators: Response of p.Ile148Asn variant
AUTHORS
Cláudia S. Rodrigues, Matilde Canto, Raquel Torres, Violeta Railean, Sofia S. Ramalho, Carlos M. Farinha, Ines Pankonien, Margarida D. Amaral
SUMMARY
Understanding how different CFTR variants affect cellular function is key to predicting disease severity, guiding genetic counseling, and choosing the right therapies for people with cystic fibrosis (CF). While current CFTR modulators mainly target the common p.Phe508del variant, rare variants like p.Ile148Asn may also respond to these drugs. This study characterized the p.Ile148Asn variant, examining its processing, trafficking, and function, as well as its response to existing modulators, suggesting potential clinical benefit for affected individuals.
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TRENDS IN MOLECULAR MEDICINE
April 2025
Cystic fibrosis at a glance: from disease mechanism to therapy
AUTHORS
Kasper Gryspeert, Laudonia L. Dipalo, Ana L. Da Silva Cunha, Mattijs Bullpen, Marjolein M. Ensinck, Marianne S. Carlon
SUMMARY
Cystic fibrosis (CF), an autosomal recessive genetic disorder, affects around 180 000 people globally, predominantly in the Caucasian population. Symptoms arise from dehydration and accumulation of thick, sticky mucus in multiple organs. Severe symptoms include chronic lung infections, bronchiectasis, and pancreatic insufficiency, which can lead to life-threatening complications. As life expectancy has increased due to improved medical care, co-morbidities such as diabetes, liver disease, and osteoporosis have arisen.
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STAR Protocols
March 2025
Protocol for functional screening of CFTR-targeted genetic therapies in patient-derived organoids using DETECTOR deep-learning-based analysis
AUTHORS
Mattijis Bulcaen, Ronald B. Lui, Kasper Gyrspeert, Sam Thierry, Anabela S. Ramalho, François Vermeulen, Xavier Casadevall I Solvas, Marianne S. Carlon
SUMMARY
Here, the research team presents a protocol for the rapid functional screening of gene editing and addition strategies in patient-derived organoids using the deep-learning-based tool DETECTOR (detection of targeted editing of cystic fibrosis transmembrane conductance regulator [CFTR] in organoids). They describe steps for wet-lab experiments, image acquisition, and CFTR function analysis by DETECTOR. They also detail procedures for applying pre-trained models and training custom models on new customized datasets.
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SCIENCE TRANSLATIONAL MEDICINE
January 2025
Undocking of an extensive ciliary network induces proteostasis and cell fate switching resulting in severe primary ciliary dyskinesia
AUTHORS
Steven L. Brody, Jiehong Pan, Tao Huang, Jian Xu, Jeffrey R. Koenitizer, Steven K. Brennan, Rashmi Nanjundappa, Thomas G. Saba, Nisreen Rumman, Andrew Berical, Finn J. Jawkins, Xiangli Wang, Rui Zhang, Moe R. Mahjoub, Amjad Horani, Susan K. Dutcher
SUMMARY
Primary ciliary dyskinesia (PCD) caused by CCDC39 or CCDC40 variants leads to more severe disease than other PCD mutations. Brody and colleagues showed that loss of the CCDC39/CCDC40 heterodimer disrupts ciliary protein networks, shifts cell fate from multiciliated to mucus-producing cells, and compromises the periciliary barrier. Restoring normal CCDC39 function in affected cells improved these defects, highlighting the potential for gene therapy in PCD.
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JOURNAL OF CYSTIC FIBROSIS
January 2025
A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function
AUTHORS
Margaret Michicich, Zachary Traylor, Caitlan McCoy, Dana M. Valerio, Alma Wilson, Molly Schneider, Sakeena Davis, Amanda Barabas, Rachel J. Mann, David F. LePage, Weihong Jiang, Mitchell L. Drumm, Thomas J. Kelley, Ronald A. Conlon, Craig A. Hodges
SUMMARY
This study introduces the first W1282X-specific mouse model of cystic fibrosis under endogenous regulatory control, demonstrating similar disease manifestations to other CF mouse models but revealing substantially different responses to therapeutic agents compared to the G542X model, underscoring the need for mutation-specific strategies and advancing the case for precision medicine in treating nonsense mutation-related CF.
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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
November 2024
Airway disease modeling with gene-edited human basal cell transplantation
AUTHORS
Andrew C. Berical, Hirofumi Kiyokawa, Mary Lou Beerman, Daniel Wallman, Gabrielle Cherfane, Victoria Dunphy, Jiehong Pan, Andrew Tilston-Lunel, Xaralabos Varelas, Amjad Horani, Steven L. Brody, Darrell N. Kotton, Finn J. Hawkins
SUMMARY
Researchers developed clonal airway basal cells (BCs) from human induced pluripotent stem cells (iPSCs) and used CRISPR-Cas9 to edit genes commonly mutated in primary ciliary dyskinesia (PCD). These edited BCs retained stem cell properties, formed differentiated mucociliary epithelium, and displayed expected ciliary defects, confirming successful gene knockout. This platform enables rapid in vitro and in vivo modeling of genotype-phenotype relationships and could accelerate therapeutic development for genetic lung diseases like PCD and cystic fibrosis.
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CELL REPORTS MEDICINE
May 2024
Prime editing functionally corrects cystic fibrosis causing CFTR mutations in human organoids and airway epithelial cells
AUTHORS
Mattijs Bulcaen, Phe´line Kortleven, Ronald B. Liu, Isabelle Sermet-Gaudelus, Anna Cereseto, Marianne S. Carlon
SUMMARY
Prime editing is a recent, CRISPR-derived genome editing technology capable of introducing precise nucleotide substitutions, insertions, and deletions. Here, we present prime editing approaches to correct L227R- and N1303K-CFTR, two mutations that cause cystic fibrosis and are not eligible for current market-approved modulator therapies. We show that, upon DNA correction of the CFTR gene, the complex glycosylation, localization, and, most importantly, function of the CFTR protein are restored in HEK293T and 16HBE cell lines. These findings were subsequently validated in patient-derived rectal organoids and human nasal epithelial cells. Through analysis of predicted and experimentally identified candidate off-target sites in primary stem cells, we confirm previous reports on the high prime editor (PE) specificity and its potential for a curative CF gene editing therapy. To facilitate future screening of genetic strategies in a translational CF model, a machine learning algorithm was developed for dynamic quantification of CFTR function in organoids (DETECTOR: ‘‘detection of targeted editing of CFTR in organoids’’).
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EUROPEAN RESPIRATORY JOURNAL
January 2024
Organoid-guided synergistic treatment of minimal function CFTR mutations with CFTR modulators, roflumilast and simvastatin: a personalized approach
AUTHORS
Sacha Spelier, Karin de Winter-de Groot, Natascha Keijzer-Nieuwenhuijze, Yves Liem, Kors van der Ent, Jeffrey Beekman, Kieke S Kamphuis
SUMMARY
This study describes how preclinical research has guided a successful personalized clinical treatment regimen in a person with minimal function CFTR, upon a synergistic treatment regimen consisting of CFTR modulators, simvastatin and roflumilast.
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MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT
January 2024
Genetic surgery for a cystic fibrosis-causing splicing mutation
AUTHORS
Mattijs Bulcaen, Marianne S. Carlon
SUMMARY
Cystic fibrosis (CF) is caused by mutations in the CFTR gene, and while therapies exist for common mutations like F508del, people with rare splicing, nonsense, or indel mutations—the “last 10%”—still lack effective treatments. Building on previous work, researchers used CRISPR-Cas9 delivered via lipid nanoparticles to correct the c.3718-2477C>T mutation, restoring normal CFTR mRNA and significantly improving CFTR function in airway cells, with no off-target effects detected in initial analyses. While further safety testing is needed for clinical use, this approach represents a promising gene-editing strategy for CF patients who remain ineligible for current modulator therapies.
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MOLECULAR THERAPY NUCLEIC ACIDS
June 2023
Nanoblades allow high-level genome editing in murine and human organoids
AUTHORS
Victor Tiroille, Adrien Krug, Emma Bokobza, Marianne S. Carlon, Frédéric Bost, Els Verhoeyen
SUMMARY
CRISPR-Cas9 gene editing in organoids has been limited by inefficient delivery methods and toxicity. This study used “nanoblade” (NB) technology to achieve high-efficiency gene knockouts—up to 75% in murine and 20–50% in human organoids—without harming the cells. NBs enable rapid, stable genome editing in organoids in just four weeks with minimal off-target effects.
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TRENDS IN MOLECULAR MEDICINE
April 2023
Readthrough compounds for nonsense mutations: riding the translational gap
AUTHORS
Sacha Speller, Eveline P.M. van Doom, Cornelis K. van der Ent, Jeffrey M. Beekman, Martijn A.J. Koppens
SUMMARY
About 10% of disease-causing mutations are nonsense mutations, which lead to severe genetic disorders with no current treatments. One common approach is to promote ribosomal readthrough of premature stop codons to restore full-length protein production. While many compounds have shown promise in preclinical studies, clinical trials have been largely unsuccessful, and this review examines the research and factors contributing to this translational gap.
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ERJ OPEN RESEARCH
January 2023
High-throughput functional assay in cystic fibrosis patient-derived organoids allows drug repurposing
AUTHORS
Sacha Speller, Eyleen de Poel, Georgia N. Ithakisiou, Sylvia W.F. Suen, Marne C. Hagemeijer, Danya Muilwijk, Annelotte M. Vonk, Jesse E. Brunsveld, Evelien Kruisselbrink, Cornelis K. van der Ent, Jeffrey M. Beekman.
SUMMARY
Cystic fibrosis (CF) therapies have improved for common mutations like F508del, but people with rare CFTR mutations, such as the nonsense mutations G542X and W1282X, still lack effective treatments. In this study, researchers miniaturized a forskolin-induced swelling (FIS) assay in intestinal organoids to screen 1,400 FDA-approved compounds for their ability to increase CFTR function in W1282X/W1282X organoids. They found that several statins, when combined with CFTR modulators, specifically and dose-dependently improved CFTR function, highlighting a potential new therapeutic approach for this mutation.
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THE JOURNAL OF CLINICAL INVESTIGATION
July 2022
Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough
AUTHORS
Rhianna E. Lee, Catherine A. Lewis, Lihua He, Emily C. Bulkin-Sullivan, Samuel C. Gallant, Teresa M. Mascenik, Hong Dang, Deborah M. Cholon, Martina Gentzsch, Lisa C. Morton, John T. Minges, Jonathan W. Theile, Neil A. Castle, Michael R. Knowles, Adam J. Kimple, Scott H. Randell
SUMMARY
Most people with cystic fibrosis (CF) can now benefit from CFTR modulators, but those with premature termination codons (PTCs) or rare CFTR variants have limited options. To study these rare variants, researchers developed Bmi-1/hTERT airway cell lines that replicated primary cell morphology and function, including responses to CFTR modulators. Using these lines, they showed that eRF3a-targeting compounds could partially restore CFTR function in PTC variants and revealed a potential new approach to treat these hard-to-treat CF mutations.
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PEDIATRIC PULMONOLOGY
May 2022
A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators
AUTHORS
Emily Kramer-Golinkoff MBE, Amanda Camacho MSW, Liza Kramer MSW, Jennifer L. Taylor-Cousar MD, MSCS, ATSF
SUMMARY
Between June 10 and July 1, 2021, Emily’s Entourage distributed a 38-question anonymous survey targeted at people with cystic fibrosis not benefitting from approved modulators via social media and email to people with CF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest. There were 431 survey respondents representing people with CF on five continents. Survey results showed that people with CF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.
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MOLECULAR THERAPY: NUCLEIC ACIDS
May 2022
Efficient suppression of endogenous CFTR nonsense mutations using anticodon-engineered transfer RNAs
AUTHORS
Wooree Ko, Joseph J. Porter, Matthew T. Sipple, Katherine M. Edwards, John D. Lueck
SUMMARY
Suppressor tRNAs have long been identified as a possible therapeutic for nonsense-associated diseases; however, their ability to inhibit nonsense-mediated mRNA decay (NMD) and support significant protein translation from endogenous transcripts has not been determined in mammalian cells. Here, we investigated the ability of anticodon edited (ACE)-tRNAs to suppress cystic fibrosis (CF) causing PTCs in the cystic fibrosis transmembrane regulator (CFTR) gene in gene-edited immortalized human bronchial epithelial (16HBEge) cells. This study establishes the ACE-tRNA approach as a potential standalone therapeutic for nonsense-associated diseases due to its ability to rescue both mRNA and full-length protein expression from PTC-containing endogenous genes.
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JOURNAL OF CYSTIC FIBROSIS
March 2022
Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids
AUTHORS
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. Koppelman, C.K. van der Ent, J.M. Beekman
SUMMARY
Pharmacotherapies for people with cystic fibrosis (pwCF) carrying premature termination codons (PTCs) in the CFTR gene were under development. Clinical studies had focused on compounds inducing translational readthrough (RT), and recent work showed that combining multiple modes of action could restore PTC function. Here, the research team assessed CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense-mediated mRNA decay (NMD), and CFTR protein modulation.
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NATURE COMMUNICATIONS 
July 2022
A multimodal iPSC platform for cystic fibrosis drug testing
AUTHORS
Andrew Berical, Rhianna E. Lee, Junjie Lu, Mary Lou Beermann, Jake A. Le Suer, Aditya Mithal, Dylan Thomas, Nicole Ranallo, Megan Peasley, Alex Stuffer, Katherine Bukis, Rebecca Seymour, Jan Harrington, Kevin Coote, Hillary Valley, Killian Hurley, Paul McNally, Gustavo Mostoslavsky, John Mahoney, Scott H. Randell, and Finn J. Hawkins
SUMMARY
A subset of individuals with cystic fibrosis do not respond to the currently available CFTR modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in induced pluripotent stem cell-derived airway cells. In both a 3-D spheroid assay using forskolin-induced swelling as well as planar cultures composed of polarized mucociliary airway epithelial cells, we detect genotype-specific differences in CFTR baseline function and response to CFTR modulators. These results demonstrate the potential of the human induced pluripotent stem cell platform as a research tool to study CF and in particular accelerate therapeutic development for CF caused by rare variants.
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (PNAS) OF THE UNITED STATES OF AMERICA
January 2022
Exon-skipping antisense oligonucleotides for cystic fibrosis therapy
AUTHORS
Young Jin Kim, Nicole Sivetz, Jessica Layne, Dillon M. Voss, Lucia Yang, Qian Zhang, Adrian R. Krainer
SUMMARY
Nonsense-mediated messenger RNA (mRNA) decay (NMD) degrades the CFTR-W1282X mRNA, leading to low levels of functional CFTR protein. A cocktail of two antisense oligonucleotides (ASOs) was developed by the study authors that promotes the skipping of exon 23 of the CFTR-W1282X mRNA. The resulting mRNA is NMD resistant and preserves the reading frame. Its translation produces CFTR-Δex23 protein that improves CFTR activity in human bronchial epithelial cells. The results set the stage for developing an ASO therapy for CF caused by the W1282X mutation.
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JOURNAL OF CYSTIC FIBROSIS
May 2021
Amphotericin B induces epithelial voltage responses in people with cystic fibrosis
AUTHORS
Rajeev S. Chorghade, Bo Ram Kim, Janice L. Launspach, Philip H. Karp, Michael J. Welsh, Martin D. Burke
SUMMARY
Marty Burke and colleagues report progression of their pioneering work to re-purpose an existing drug – Amphotericin B (AmB) – as a mutation agnostic therapy for CF. Prior studies in cell and animal models demonstrated that AmB effectively mimics key functions of the CFTR ion channel. In this study, the ability of AmB to alter nasal potential difference (NPD) – a clinical biomarker used to assess efficacy of potential CF therapies – in people with CF. In eight CF subjects not using modulators, AmB mediated NPD changes consistent with AmB recapitulating CFTR activity and similar to the effect of ivacaftor in CF subjects with the G551D-CFTR mutation.
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CELL STEM CELL
January 2021
Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells
AUTHORS
Finn J. Hawkins, Shingo Suzuki, Mary Lou Beerman, Steven L. Brody, Brian R. Davise, Darrell N. Kotton
SUMMARY
Proof-of-concept studies that demonstrate pharmacological repair of CFTR function in nasal epithelial cells derived from CF subjects with the W1282X-CFTR mutation. Robust restoration of CFTR activity was observed with CFTR modulators in combination with an inhibitor of non-sense mediate degradation (NMD), a process that recognizes and destroys transcripts containing nonsense mutations (‘X mutations’).
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JOURNAL OF CYSTIC FIBROSIS
September 2020
Functional rescue of c.3846G>A (W1282X) in patient-derived nasal cultures achieved by inhibition of nonsense mediated decay and protein modulators with complementary mechanisms of action
AUTHORS
Onofrio Laselva, Paul D.W. Eckford, Claire Bartlett, Hong Ouyang, Tarini N.A. Gundawardena, Tanja Gonska, Theo J. Moraes, Christin E. Bear
SUMMARY
In this study, the research team directed human induced pluripotent stem cells (iPSCs) to become airway basal cells, a key stem cell population of the airway epithelium. These lab-grown cells can self-renew, differentiate into multiple airway cell types, and model features of diseases like asthma, cystic fibrosis, and primary ciliary dyskinesia, offering a powerful tool for studying airway disorders and advancing regenerative medicine.
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PEDIATRIC PULMONOLOGY
July 2020
Ataluren/ivacaftor combination therapy: Two N-of-1 trials in cystic fibrosis patients with nonsense mutations
AUTHORS
Jacelyn E. Peabody Lever, Venkateshwar Mutyam, Heather Y. Hathorne, Ning Peng, Jyoti Sharma, Lloyd J. Edwards, Steven M. Rowe
SUMMARY
Clinical study testing the hypothesis that ivacaftor in combination with the readthrough drug ataluren could be beneficial for CF subjects with nonsense mutations. No meaningful benefit was observed in two subjects, with ivacaftor or ivacaftor and ataluren; however, some benefits were observed of unknown significance, including minor increases in lung function and body mass index.
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SCIENTIFIC REPORTS
November 2019
Nanomolar-potency ‘co-potentiator’ therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants
AUTHORS
Puay-wah Phuan, Joseph-Anthony Tan, Amber A. Rivera, Lorna Zlock, Dennis W. Nielson, Walter E. Finkbeiner, Peter M. Haggie, Alan S. Verkman
SUMMARY
High throughput screening is used to identify four additional classes of co-potentiators, CFTR modulators that work together with existing potentiators such as Ivacaftor to activate several rare CFTR mutants including CFTR1281 (the protein product generated by the. W1282X mutation) and N1303K-CFTR. These studies represent continued progression of a novel modulator paradigm that could have therapeutic utility for several rare CFTR mutations with no currently available therapy.
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NATURE
March 2019
Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia
AUTHORS
Katrina A. Muraglia, Rajeev S. Chorghade, Bo Ram Kim, Xiao Xiao Tang, Viral S. Shah, Anthony S. Grillo, Page N. Daniels, Alexander G. Cioffi, Philip H. Karp, Lingyang Zhu, Michael J. Welsh, Martin D. Burke
SUMMARY
Pioneering work by Marty Burke, University of Illinois Urbana-Champaign, to develop a new CF therapy by re-purposing an existing drug – Amphotericin B. In collaboration with the University of Iowa, studies in the CF pig revealed the potential therapeutic benefit of Amphotericin B in restoring lung immune defense mechanisms.
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NATURE COMMUNICATIONS
February 2019
Engineered transfer RNAs for suppression of premature termination codons
AUTHORS
John D. Lueck, Jae Seok Yoon, Alfredo Perales-Puchalt, Adam L. Mackey, Daniel T. Infield, Mark A. Behlke, Marshall R. Pope, David B. Weiner, William R. Skach, Paul B. McCray Jr., Christopher A. Ahern
SUMMARY
Therapeutic development of transfer RNAs (tRNAs) to recognize disease-causing nonsense mutations – such as W1282X – in the CFTR gene and permit synthesis of full length CFTR protein. This project was lead by Chris Ahern and John Lueck at the University of Iowa and involved scientists at The Wistar Institute in Philadelphia, PA, and The CFF Therapeutics lab in Lexington, MA. Project progression remains a priority of Emily’s Entourage with funding for James Dhalman at Georgia Tech to work on delivering therapeutic tRNAs to the lung.
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JOURNAL OF CYSTIC FIBROSIS
September 2018
Combination potentiator (co-potentiator’) therapy for CF caused by CFTR mutants, including N1303K, that are poorly responsive to single potentiators
AUTHORS
Puay-Wah Phuan, Jung-Ho Son, Joseph-Anthony Tan, Clarabella Li, Ilaria Musante, Loma Zlock, Dennis W. Neilson, Walter E. Finkbeiner, Mark J. Kurth, Luis J. Galietta, Peter M. Haggie, Alan S. Verkman
SUMMARY
A second manuscript for the Verkman group, at the University of California, San Francisco, extends the concept of using Ivacaftor with a second potentiator (a co-potentiator) to significantly elevate the activity of a second rare CFTR mutation (N1303K). Importantly, this study also includes the first demonstration that W1282X-CFTR can be activated by Ivacaftor and a co-potentiator in human nasal epithelial cells.
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JOURNAL OF CYSTIC FIBROSIS
January 2017
Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation
AUTHORS
Venkateshwar Mutyam, Emily Falk Libby, Ning Peng, Denis Hadjiliadis, Michael Bonk, George M. Solomon, Steven M. Rowe
SUMMARY
Clinical study conducted by Steven M. Rowe MD at University of Alabama at Birmingham that demonstrated significant therapeutic benefit of using Ivacaftor (VX-770) in a W1282X homozygous CF subject. The clinical benefits – reduced pulmonary exacerbations, weight gain, reduced insulin usage – support off-label use of this CF drug in W1282X CF subjects.
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THE JOURNAL OF BIOLOGICAL CHEMISTRY
January 2017
Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product
AUTHORS
Peter M. Haggie, Puay-Wah Phuan, Joseph-Anthony Tan, Haijin Xu, Radu G. Avramescu, Doranda Perdomo, Lorna Zlock, Dennis W. Nielson, Walter E. Finkbeiner, Gergely L. Lukacs, Alas S. Verkman
SUMMARY
Drug discovery project conducted at University of California, San Francisco (UCSF) by Alan Verkman, MD, PhD. The study identified potent ‘correctors’ and ‘potentiators’ for the truncated form of CFTR produced by the W1282X mutation, and validated a therapeutic approach for the W1282X mutation similar to that used for delF508.
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