[{"data":1,"prerenderedAt":289},["ShallowReactive",2],{"newsletter-\u002Fnewsletter\u002Fcftr":3},{"id":4,"title":5,"author":6,"body":7,"date":280,"description":281,"extension":282,"meta":283,"navigation":284,"path":285,"seo":286,"stem":287,"__hash__":288},"newsletter\u002Fnewsletter\u002Fcftr.md","The “New Kid” of Medicine: CFTR Modulator Therapies","Shereen Ali",{"type":8,"value":9,"toc":267},"minimark",[10,15,31,35,39,42,59,63,66,69,92,96,99,107,114,117,120,124,127,130,133,137,140,143,146,152,158,174,189,201,215,226,240,254],[11,12,14],"h2",{"id":13},"in-brief","In Brief",[16,17,18,22,25,28],"ul",{},[19,20,21],"li",{},"Cystic Fibrosis (CF) is an inherited genetic disorder causing thick, sticky mucus to accumulate in the lungs and digestive system",[19,23,24],{},"CF is caused by a mutation in the CFTR gene, which affects salt and water balance in cells",[19,26,27],{},"CFTR modulator therapies are oral drugs that fix the malfunctioning CFTR protein",[19,29,30],{},"Correctors help the protein fold correctly and potentiators help the protein channel open",[11,32,34],{"id":33},"introduction","Introduction",[36,37,38],"p",{},"Buddhist monk and peace activist Thich Nhat Hanh said \"breath is the bridge which connects life to consciousness, which unites your body to your thoughts.\" The act of breathing restores the connection between physical sensations and mental states. This is something most of us never think twice about. But for roughly 1 in 25 Americans, every breath is a conscious, labored effort. These are people living with Cystic Fibrosis (CF), a disease that turns one of the body's most automatic functions into a daily struggle.",[36,40,41],{},"Cystic Fibrosis is an inherited genetic disorder causing thick, sticky mucus to accumulate in the lungs and digestive system, resulting in severe organ damage and frequent infections.  It is one of the most common genetic diseases among Caucasian populations–though it affects individuals of all racial and ethnic backgrounds–with approximately 40,000 children and adults in the United States and an estimated 100,000 to 160,000 people globally (Scotet). However, despite the significant number of infected individuals, an effective cure has yet to be developed. Significant research gaps exist, primarily driven by genetic exclusivity, varying clinical responses, long-term safety profiles, and prohibitive global healthcare costs. This is where modulator therapies come in.",[43,44,46,47,46,54],"div",{"style":45},"display: flex; justify-content: center; align-items: center; gap: 20px;","\n  ",[48,49],"img",{"src":50,"alt":51,"className":52},"\u002Fnewsletter\u002Fcftr\u002Fcf.png","Cystic Fibrosis Depiction",[53],"rounded-lg",[48,55],{"src":56,"alt":57,"className":58},"\u002Fnewsletter\u002Fcftr\u002Fcases.png","Cystic Fibrosis Cases",[53],[11,60,62],{"id":61},"cftr-modulator-therapies","CFTR Modulator Therapies",[36,64,65],{},"CFTR modulator therapies are transformative oral drugs that treat the underlying cause of CF by fixing the malfunctioning CFTR protein, rather than just managing the symptoms. These therapies improve lung function, weight (BMI), and quality of life for people with specific CF mutations. For over 90% of CF patients with specific genetic mutations, these drugs significantly slow disease progression and extend lifespans (Chun). The most surprising part? They’re fresh off the boat. First introduced in 2012, it was a major breakthrough. It holds the title as the first drug to target the foundational factor of Cystic Fibrosis rather than just its symptoms. In 2019, key modulator Elexacaftor\u002Ftezacaftor\u002Fivacaftor (Trikafta) was approved. It is a modulator different from the ones that preceded it, treating approximately 90% of cystic fibrosis patients, including those with just one copy of the F508del mutation (Rubin).",[36,67,68],{},"Cystic Fibrosis is caused by a mutation in the CFTR gene, which affects salt and water balance in cells (by producing a dysfunctional protein that fails to transport chloride and water across cell membranes). Thus, modulator therapies work by allowing chloride to move into cells, keeping mucus thin and preventing buildup in organs. There are two main types: correctors (help the protein fold correctly and reach the cell surface) and potentiators (help the protein channel open).",[43,70,46,74,46,79],{"className":71},[72,73],"flex","gap-20",[48,75],{"src":76,"alt":77,"className":78},"\u002Fnewsletter\u002Fcftr\u002Fapproval.png","CFTR Approval",[53],[43,80,85,86,85,89],{"className":81},[72,82,83,84],"flex-col","items-center","justify-center","\n    ",[36,87,88],{},"Restoration of CFTR function has been associated with improved airway surface hydration and addition to increased airway surface fluid pH",[36,90,91],{},"CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis”, Saluzzo, 2022, NCBI",[11,93,95],{"id":94},"potentiators","Potentiators",[36,97,98],{},"The CFTR protein functions like a channel or tunnel with a gate that controls the movement of chloride ions. Potentiators are a type of CFTR modulator that keep this gate open, allowing chloride to pass more easily through the cell membrane.",[36,100,101],{},[48,102],{"alt":103,"className":104,"src":105,"style":106},"Potentiators in the cell",[53],"\u002Fnewsletter\u002Fcftr\u002Fprotein.png","display: block; margin-inline: auto;",[36,108,113],{"className":109},[110,111,112],"text-sm","text-neutral-700","text-center","(Han)",[36,115,116],{},"Ivacaftor (Kalydeco) is an example of a potentiator. It is beneficial for people with gating and conduction mutations, as well as certain residual function and splice mutations that result in reduced amounts of normal CFTR protein (MedChemExpress). In these types of mutations, some CFTR protein is able to reach the cell surface, but either the quantity is too low or the protein does not transport enough chloride across the membrane.",[36,118,119],{},"By increasing the amount of time the CFTR channel remains open, potentiators enhance chloride movement through the cell membrane. This improved chloride transport helps restore CFTR function and can reduce the symptoms associated with cystic fibrosis.",[11,121,123],{"id":122},"correctors","Correctors",[36,125,126],{},"Corrector medications help the CFTR protein fold into its proper three-dimensional structure, allowing it to travel, or “traffic,” to the cell surface where it can function.",[36,128,129],{},"Approximately 85% of individuals with Cystic Fibrosis carry at least one copy of the F508del mutation (Editorial). This mutation causes the CFTR protein to misfold, preventing it from developing the correct shape. Corrector therapies improve the protein’s folding, help it reach the cell surface, and increase the amount of time it remains there. However, these drugs cannot fully correct the folding defect, so only a portion of the CFTR proteins successfully reach the cell membrane. In addition, the proteins that do arrive at the surface do not open effectively enough to allow adequate chloride transport out of the cell.",[36,131,132],{},"When a corrector is combined with a potentiator, such as ivacaftor, the potentiator helps keep the CFTR channel open. This allows more chloride to move through the channel, which can help lessen the symptoms of CF.",[11,134,136],{"id":135},"conclusion","Conclusion",[36,138,139],{},"Ultimately, CFTR modulator therapies have revolutionized the treatment of Cystic Fibrosis by addressing the root cause of the disease rather than simply treating its indicators.",[36,141,142],{},"The research and information of these modulators would not have been possible without the courage of the patients who participated in clinical trials and chose to use these new therapies despite the uncertainties involved. As research continues and new modulators are developed, there is growing hope that people with Cystic Fibrosis will be able to live longer, healthier lives. The progress made through CFTR modulator therapies demonstrates how innovation and perseverance can work together to change the future of a disease that once had very limited treatment options.",[144,145],"hr",{},[147,148,151],"h3",{"className":149,"id":150},[112],"works-cited","Works Cited",[144,153],{"className":154},[155,156,157],"border-cyan-700","mx-auto","max-w-[80cqw]",[36,159,160,161,165,166,173],{},"Chalmers, Sarah. “Cystic Fibrosis.” ",[162,163,164],"em",{},"Mayo Clinic",", Mayo Clinic, 7 Dec. 2024, ",[167,168,172],"a",{"href":169,"rel":170},"https:\u002F\u002Fwww.mayoclinic.org\u002Fdiseases-conditions\u002Fcystic-fibrosis\u002Fsymptoms-causes\u002Fsyc-2035370",[171],"nofollow","www.mayoclinic.org\u002Fdiseases-conditions\u002Fcystic-fibrosis\u002Fsymptoms-causes\u002Fsyc-2035370",".",[36,175,176,177,180,181,184,185,173],{},"Chun, Stanford W., et al. “Highly Effective Cystic Fibrosis Transmembrane Conductance (Regulator) Modulator Therapy: Shifting the Curve for Most While Leaving Some Further Behind.” ",[162,178,179],{},"Current Opinion in Pediatrics",", vol. 36, no. 3, 2024, pp. 290–295. ",[162,182,183],{},"PubMed",", ",[167,186,187],{"href":187,"rel":188},"https:\u002F\u002Fdoi.org\u002F10.1097\u002FMOP.0000000000001384",[171],[36,190,191,192,195,196,173],{},"Editorial Team. “How Does Cystic Fibrosis Develop?” ",[162,193,194],{},"Cystic-Fibrosis.com",", 15 Aug. 2019, ",[167,197,200],{"href":198,"rel":199},"https:\u002F\u002Fcystic-fibrosis.com\u002Fpathophysiology",[171],"cystic-fibrosis.com\u002Fpathophysiology",[36,202,203,204,207,208,184,211,173],{},"Han, Xiao Xuan, et al. “Recommended Tool Compounds for Modifying the Cystic Fibrosis Transmembrane Conductance Regulator Channel Variants.” ",[162,205,206],{},"ACS Pharmacology & Translational Science",", vol. 7, no. 4, 14 Mar. 2024, pp. 1021–1035. ",[162,209,210],{},"ACS Publications",[167,212,213],{"href":213,"rel":214},"https:\u002F\u002Fdoi.org\u002F10.1021\u002Facsptsci.3c00362",[171],[36,216,217,218,184,221,225],{},"MedChemExpress. “CFTR Targets.” ",[162,219,220],{},"MedChemExpress",[167,222,223],{"href":223,"rel":224},"https:\u002F\u002Fwww.medchemexpress.com\u002FTargets\u002FCFTR.html",[171],". Accessed 16 Aug. 2026.",[36,227,228,229,232,233,184,236,173],{},"Rubin, Jaime L., et al. “Impact of CFTR Modulators on Longitudinal Cystic Fibrosis Survival and Mortality: Review and Secondary Analysis.” ",[162,230,231],{},"Pulmonary Therapy",", vol. 11, no. 3, 2025, pp. 365–386. ",[162,234,235],{},"SpringerLink",[167,237,238],{"href":238,"rel":239},"https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs41030-025-00303-4",[171],[36,241,242,243,246,247,184,250,173],{},"Saluzzo, Francesca, et al. “CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis.” ",[162,244,245],{},"Cells",", vol. 11, no. 7, 6 Apr. 2022, art. 1243. ",[162,248,249],{},"MDPI",[167,251,252],{"href":252,"rel":253},"https:\u002F\u002Fdoi.org\u002F10.3390\u002Fcells11071243",[171],[36,255,256,257,260,261,184,263,173],{},"Scotet, Virginie, et al. “The Changing Epidemiology of Cystic Fibrosis: Incidence, Survival and Impact of the CFTR Gene Discovery.” ",[162,258,259],{},"Genes",", vol. 11, no. 6, 26 May 2020, art. 589. ",[162,262,249],{},[167,264,265],{"href":265,"rel":266},"https:\u002F\u002Fdoi.org\u002F10.3390\u002Fgenes11060589",[171],{"title":268,"searchDepth":269,"depth":269,"links":270},"",2,[271,272,273,274,275,276],{"id":13,"depth":269,"text":14},{"id":33,"depth":269,"text":34},{"id":61,"depth":269,"text":62},{"id":94,"depth":269,"text":95},{"id":122,"depth":269,"text":123},{"id":135,"depth":269,"text":136,"children":277},[278],{"id":150,"depth":279,"text":151},3,"2026-06-29","CFTR Modulator therapies are some of the best tools we have against Cystic Fibrosis, that attack the disease at its heart.","md",{"image":50},true,"\u002Fnewsletter\u002Fcftr",{"title":5,"description":281},"newsletter\u002Fcftr","5-BarSFD6jiSGM8uToGw0-0cyDKCDgKQwVVMzp2A3jE",1789320737616]