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Advancements in CFTR Modulators for Cystic Fibrosis Treatment – Mutations
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category-cystic-fibrosis tag-cftr-modulators tag-cftr-protein tag-cystic-fibrosis tag-cystic-fibrosis-medication tag-cystic-fibrosis-supportive-therapy tag-cystic-fibrosis-treatment tag-hypothyroidism tag-phenylketonuria" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="2560" height="1340" src="https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-scaled.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" srcset="https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-scaled.jpg 2560w, https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-300x157.jpg 300w, https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-1024x536.jpg 1024w, https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-768x402.jpg 768w, https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-1536x804.jpg 1536w, https://mutation.blog/archive/wp-content/uploads/2024/09/image-_28_-min-2048x1072.jpg 2048w" sizes="(max-width: 2560px) 100vw, 2560px" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">Advancements in CFTR Modulators for Cystic Fibrosis Treatment</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-09-10T18:24:46+05:30" itemprop="datePublished">September 10, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://mutation.blog/archive/author/mutation/" title="View all posts by mutation" rel="author" itemprop="url"><span class="author-name" itemprop="name">mutation</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <p><b><span style="font-weight: 400;">C</span></b><span style="font-weight: 400;">ystic fibrosis is one of the hereditary diseases that run through genetics and, until now, was one of the biggest challenges to patients and doctors. This germinal multicystic illness with a mimicked name of genetic origin affecting an estimated ten thousand persons in the world population is brought about by DNA defects in the CFTR gene. It relates to a disease involving a protein that is so essential in the movement of chloride ions across cell membranes; this brings the formation of thick and sticky mucus and thus respiratory and digestive problems. This has been the case for a long time since the main treatment that was available for CF patients only involved administering a technique that was solely meant to manage the symptoms of the illness without thinking of any cure for the disease. However, the new development in the CFTR modulators is making significant alterations in the management of pulmonary CMC because, with this effective therapy, patients with the aforementioned chronic disease not only get to increase their lifespan but also get improved quality of life.</span></p> <h3><b>Understanding CFTR Modulators</b></h3> <p><span style="font-weight: 400;">CFTR modulators are drugs that can treat the impaired working of the CFTR protein. These kinds of modulators are grouped based on what aspect of the CFTR that is not usual they focus on. These main categories are potentiators, correctors, and amplifiers. Potentiators enhance the function of CFTR at the cell surface, while correctors help in the folding and transport of this protein to the cell surface; for their part, amplifiers increase the synthesis of this CFTR protein.</span></p> <p><span style="font-weight: 400;">Ivacaftor is also a potentiator used in the treatment of cystic fibrosis; this was another major step in the modulation of CFTR. The studies have demonstrated a high level of effectiveness in the enhancement of lung function, reduction of pulmonary episodes, and enhancement of the quality of life among patients diagnosed with certain mutations in the specific CFTR gene. Clinical trials have revealed that ivacaftor, which has the effect of enhancing mean predicted FEV1% pred, which is a lung function measurement, was increased and the sweat chloride concentration was also reduced, which demonstrates the improved activity of CFTR. In the case of ivacaftor, medicine moved from managing the disease to addressing basic needs regarding the disease, which is cystic fibrosis (CF).</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://mutation.blog/publication-trends/index/cystic fibrosis" target="_blank" title="cystic fibrosis - yearwise publication trends">cystic fibrosis</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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The leading edge of these advancements is VX-659 and VX-445 when used in combination with ivacaftor and ivacaftor. These triple combination therapies have been tested in clinical trials with results showing significant improvement in CFTR protein processing, trafficking, and functioning, which leads to major improvements in people having one or two F508del CFTR alleles in which their health status was significantly advanced. Since then, these treatments have been linked with a marked increase in FEV1, decreased pulmonary exacerbations, and improved quality of life scores.</span></p> <p><span style="font-weight: 400;">Another very significant addition to the CFTR modulation is the combination of ivacaftor and lumacaftor. Lumacaftor functions as a corrector, which helps in the proper folding of CFTR protein, while ivacaftor increases its functionality on the cell surface. This combination has shown effectiveness in patients who are homozygous for the F508del mutation, the most common cause of CF. It has been established that lung function improves with lumacaftor-ivacaftor therapy; it decreases exacerbations in pulmonary conditions as well as enhances overall respiratory health. Indeed, there have been remarkable advantages from this mixed treatment, despite some effects like chest tightness and dyspnea.</span></p> <h3><b>Treatment Options are Increased</b></h3> <p><span style="font-weight: 400;">The ivacaftor-ivacaftor combination is one such treatment option for CFTR with residual-function mutations. Studies have revealed that this blend has an improved profile of safety as well as increasing the measures of FEV1 and quality of life. This mix is particularly significant for patients with a residual function mutation who are heterozygous for the Phe508del mutation, thus widening the range of those who would benefit from CFTR modulators.</span></p> <p><span style="font-weight: 400;">Data from cystic fibrosis registries in the US and UK have provided long-term benefits of CFTR modulators. Observational studies show that ivacaftor considerably reduces hospitalizations, transplantation, death, and pulmonary exacerbations over time. Meanwhile, ivacaftor-treated patients also had lower rates of complications related to CF and reduced presence of pathogens, as well as preservation of lung function. These data clarify the transformational significance CFTR modulators have on the progression of illness in both individuals and populations.</span></p> <h3><b>Rapid Advances in Therapeutic as well as Future Directions</b></h3> <p><span style="font-weight: 400;">The development of CFTR modulators is a rapidly advancing field, and next-generation modulators with even higher efficacy and safety are currently under study. Studies on new combinations and formulations of existing modulators are on their way, and wholly new classes of pharmaceuticals against rare CFTR mutations are being explored to open up additional ways for personalized treatment. The goal should be to develop therapies that can correct the underlying defect of more CFTR mutations to enable more effective and personalized treatments for all CF patients.</span></p> <p><span style="font-weight: 400;">Among the more prominent challenges with CFTR modulators, though promising, are issues related to access to these treatments and their affordability in all patients. CFTR modulators are extremely expensive, and that poses a major barrier, especially for lower- and middle-income countries. Further, continuous follow-up to safety and efficacy in the long run and further research are required to define the full potential but also limitations of these treatments.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://mutation.blog/recent-publications/index/cystic fibrosis" target="_blank" rel="noopener" title="cystic fibrosis - yearwise publication list">cystic fibrosis</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .author-main { border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .publication-block { padding: 10px; margin-bottom: 10px; background-color: #f9f9f9; text-align: left; background: #FFF; border-bottom: solid 1px #ccc; margin-left: 15px; margin-right: 15px; } .publication-block h3 { margin: 0 0 10px; color: #000!important; } .publication-block a { font-size: 16px !important; line-height: 1em; font-weight: 600; text-transform: none; color: #000; padding: 0px; } .publication-block a:hover{ color: #227cdc; text-decoration:underline; } .article-scroll { max-height: 445px; overflow-y: auto; overflow-x: hidden; } ::-webkit-scrollbar-track { -webkit-box-shadow: inset 0 0 6px rgba(0,0,0,0.3); background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar { width: 6px; background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar-thumb { background-color: #ababab; border-radius:30px; } .publication-block p { margin-bottom: .5em; font-size: 15px; color: #000; } h3 { font-size: 18px !important; margin-bottom: 20px; line-height: 1.2em; font-weight: 600; text-transform: none; } a { padding: 5px; color: #a71c49; } #keyword-papers{ margin-top: 20px; text-align: center; } </style> <script> function decodeString(str) { str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); return str; } function displayResults_recent(papers) { var resultsContainer = document.getElementById('results_recent'); if (!papers || papers.length === 0) { resultsContainer.innerHTML = '<p>No recent publications found.</p>'; return; } papers.forEach(paper => { var publicationBlock = document.createElement('div'); publicationBlock.className = 'publication-block'; var title_de = decodeString(paper.title); var publicationHTML = ` <div style="margin-bottom: 10px;line-height: 24px;"><a href="${paper.url}" target="_blank" title="${title_de}">${title_de}</a></div> <p><strong>Issue Release:</strong> ${paper.publishedDate}</p> `; publicationBlock.innerHTML = publicationHTML; resultsContainer.appendChild(publicationBlock); }); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://mutation.blog/recent-publications/index/${key_replace}" target="_blank" title="${key} - publication list">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var recent_papers = [ { "title": "Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946716", "publishedDate": "2024" }, { "title": "Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator (CFTR) correctors VX-445 and VX-121.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38954478", "publishedDate": "2024" }, { "title": "[Fibrophysematous lung changes and microbiota changes in senile persons.]", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38944785", "publishedDate": "2024" }, { "title": "Cell type-specific expression of angiotensin receptors in the human lung with implications for health, aging, and chronic disease.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38948835", "publishedDate": "2024" }, { "title": "Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38844921", "publishedDate": "2024" }, { "title": "Saccharomyces cerevisiae \u03b2-glucan improves the response of trained macrophages to severe P. aeruginosa infections.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38850343", "publishedDate": "2024" }, { "title": "Challenges to the optimisation of cystic fibrosis exacerbation treatment outcomes.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38843940", "publishedDate": "2024" }, { "title": "Clinical outcomes of two infants with cystic fibrosis, including presence of the vas deferens, born to a woman with cystic fibrosis taking CFTR modulators during both pregnancies.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38876833", "publishedDate": "2024" }, { "title": "Interdomain communication in a homodimeric ABC transporter.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38844133", "publishedDate": "2024" }, { "title": "Sex differences persist after treatment with ivacaftor in people with cystic fibrosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38871282", "publishedDate": "2024" }, { "title": "Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38246828", "publishedDate": "2024" }, { "title": "Culture-independent Multilocus sequence typing screening for Haemophilus influenzae cross-infection in non-cystic fibrosis bronchiectasis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38878342", "publishedDate": "2024" }, { "title": "Detection of cytokines in nasal lavage samples of patients with cystic fibrosis: comparison of two different cytokine detection assays.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38890643", "publishedDate": "2024" }, { "title": "Re:\u00a0Characteristics and Outcomes of Patients with Cystic Fibrosis and Pancreatic Cancer: A Large Database Analysis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38888728", "publishedDate": "2024" }, { "title": "Cefiderocol susceptibility of Achromobacter spp.: study of an accurately identified collection of 230 strains.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38886694", "publishedDate": "2024" }, { "title": "Targeting ubiquitination machinery in cystic fibrosis: Where do we stand?", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38888668", "publishedDate": "2024" }, { "title": "Investigation of F508del CFTR unfolding and a search for stabilizing small molecules.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38876247", "publishedDate": "2024" }, { "title": "Standards for the care of people with cystic fibrosis (CF); recognising and addressing CF health issues.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38233247", "publishedDate": "2024" }, { "title": "Point of care lung ultrasound in preschool children with cystic fibrosis: a case-controlled, prospective, pilot study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38240960", "publishedDate": "2024" }, { "title": "The solute carrier family 26 member 9 modifies rapidly progressing cystic fibrosis associated with homozygous F508del CFTR mutation.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38852790", "publishedDate": "2024" } ]; var keywordsArray = ["Cystic fibrosis","Ivacaftor","Lumacaftor","Tezacaftor","VX-659","VX-445 triple combination therapy","F508del","innovation in cystic fibrosis"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h3><b>Conclusion</b></h3> <p><span style="font-weight: 400;">It is considered that the CFTR modulators introduced have created a paradigm shift in the treatment of cystic fibrosis. And from the novel insulin to triple-combination therapies and further on, changing the lives of those with CF by tackling the root of the issue. Where the research continues to move forward at such a rapid pace, extremely competent and detailed interventions may be on the horizon, which would allow one to continue forward without cystic fibrosis as a debilitating disease in the future. This account of the story of CFTR modulation is a perfect example in terms of harnessing the progress of scientific development around the world and especially the scourge of always trying to achieve even further improvement in everyone’s health.</span></p> <p></p> <h3><b>References</b></h3> <ol> <li>Davies, J.C., Moskowitz, S.M., Brown, C., Horsley, A., Mall, M.A., McKone, E.F., Plant, B.J., Prais, D., Ramsey, B.W., Taylor-Cousar, J.L. and Tullis, E., 2018. <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1807119">VX-659–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles.</a> <i>New england journal of medicine</i>, <i>379</i>(17), pp.1599-1611.</li> <li>Taylor-Cousar, J.L., Mall, M.A., Ramsey, B.W., McKone, E.F., Tullis, E., Marigowda, G., McKee, C.M., Waltz, D., Moskowitz, S.M., Savage, J. and Xuan, F., 2019. <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1807119">Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles.</a> <i>ERJ open research</i>, <i>5</i>(2).</li> <li>Keating, D., Marigowda, G., Burr, L., Daines, C., Mall, M.A., McKone, E.F., Ramsey, B.W., Rowe, S.M., Sass, L.A., Tullis, E. and McKee, C.M., 2018. <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1807120">VX-445–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles.</a> <i>New england journal of medicine</i>, <i>379</i>(17), pp.1612-1620.</li> <li>Clancy, J.P., 2018. <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/ppul.24157">Rapid therapeutic advances in CFTR modulator science</a>. <i>Pediatric pulmonology</i>, <i>53</i>(S3), pp.S4-S11.</li> <li>Bessonova, L., Volkova, N., Higgins, M., Bengtsson, L., Tian, S., Simard, C., Konstan, M.W., Sawicki, G.S., Sewall, A., Nyangoma, S. and Elbert, A., 2018. <a href="https://thorax.bmj.com/content/73/8/731.abstract">Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. </a><i>Thorax</i>, <i>73</i>(8), pp.731-740.</li> <li>Rowe, S.M., Daines, C., Ringshausen, F.C., Kerem, E., Wilson, J., Tullis, E., Nair, N., Simard, C., Han, L., Ingenito, E.P. and McKee, C., 2017. <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1709847">Tezacaftor–ivacaftor in residual-function heterozygotes with cystic fibrosis.</a> <i>New England Journal of Medicine</i>, <i>377</i>(21), pp.2024-2035.</li> <li>Rowe, S.M., McColley, S.A., Rietschel, E., Li, X., Bell, S.C., Konstan, M.W., Marigowda, G., Waltz, D. and Boyle, M.P., 2017. <a href="https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201609-689OC">Lumacaftor/ivacaftor treatment of patients with cystic fibrosis heterozygous for F508del‐CFTR.</a> <i>Annals of the American Thoracic Society</i>, <i>14</i>(2), pp.213-219.</li> </ol> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Top Experts on “<b style="color:#000;font-size:22px;">cystic fibrosis</b>“</h2> </div> </div><div class="author-main"><div id="results_author"></div><div style="text-align: center;"><a class="register-button" href="https://mutation.blog/expert-search" target="_blank" rel="noopener">Find experts on any field</a></div></div><div class="inside-article" style="background: none;border: none;box-shadow: none;margin-top: -70px;"> <style> .author-block { padding: 15px; 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