Cystic fibrosis: new challenges and perspectives beyond elexacaftor/tezacaftor/ivacaftor

Therapeutic Advances in Respiratory Disease, Journal Year: 2025, Volume and Issue: 19

Published: March 1, 2025

Over the past decade, major clinical advances have been made in healthcare and therapeutic development for cystic fibrosis (CF), a lethal genetic disease caused by mutations gene encoding CF transmembrane conductance regulator (CFTR) protein. CFTR modulators represent innovative treatments that directly target primary defects mutated protein demonstrated significant benefits many people with (pwCF) who are eligible these treatments. In particular, triple combination therapy composed of elexacaftor, tezacaftor, ivacaftor (ETI) has changed landscape significantly improving lung function, quality life, predicted survival rates. Here, we provided comprehensive summary impact ETI on outcomes need further research long-term efficacy, side effects, pregnancy, possible drug–drug interactions, extra-pulmonary manifestations. Moreover, number pwCF unresponsive to drugs or cannot afford their high costs. We, therefore, discussed health inequity issues alternative strategies under aiming obtain effective therapies all pwCF.

Language: Английский

---

Behavioural and sleep issues after initiation of elexacaftor–tezacaftor–ivacaftor in preschool-age children with cystic fibrosis

The Lancet, Journal Year: 2024, Volume and Issue: 404(10448), P. 117 - 120

Published: June 28, 2024

Language: Английский

---

Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least One F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor

The Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 274, P. 114176 - 114176

Published: June 28, 2024

Language: Английский

---

Tezacaftor is a direct inhibitor of sphingolipid delta-4 desaturase enzyme (DEGS)

Journal of Cystic Fibrosis, Journal Year: 2024, Volume and Issue: 23(6), P. 1167 - 1172

Published: May 24, 2024

Language: Английский

---

Mental disorders in patients with cystic fibrosis

The Clinician, Journal Year: 2025, Volume and Issue: 18(4), P. 12 - 19

Published: Jan. 26, 2025

Introduction. Cystic fibrosis (CF) is a genetic disease that leads to dysfunction of internal organs and significantly increases the risk respiratory infections. According N. P. Bochkov Medical Genetic Research Center, 1 out 9,000 newborns suffers from CF. Chronic has negative impact on mental health can contribute developmentof anxiety depressive disorders, as well accentuated traits personality disorders. Aim. To summarize currently available data disorders in patients with CF, current recommendations regarding management this disease. Materials methods. Articles were searched Google Scholar databases, eLIBRARY.ru, Elsevier, PubMed 2014 2024 by key words Russian English accordance purpose study. Results. It been established problems are associated worse compliance treatment, difficulties self-organization self-care. Some hypotheses explain pathogenesis have provided. The characteristics course clinical presentation group described. potential for treatment provided, taking into account specificities metabolism psychotropic drugs people tactics management, including creation multidisciplinary team would consist doctor somatic profile, psychiatrist psychologist. A strategy development aspect medical care CF also proposed. Conclusion. Drawing attention scientific community problem will allow introduction methods monitoring status early detection symptoms, entail teams,

Language: Английский

---

Psychosocial and mental health in cystic fibrosis in the modern era of care: time to evolve

BMJ Open Respiratory Research, Journal Year: 2025, Volume and Issue: 12(1), P. e002606 - e002606

Published: Feb. 1, 2025

Cystic fibrosis (CF) treatment has revolutionised care over the past three decades with major advances in survival. Despite these advances, CF continues to create psychological and social challenges for people (PWCF) throughout their life is associated worse health outcomes higher healthcare costs. Anxiety depression screening management protocols are widely implemented within care; however, a much broader scope of psychosocial exist which lack standardised approach. The advent transmembrane conductance regulator modulator therapies transforming landscape PWCF new evolving needs. What it means have CF, expectations, hopes stressors rapidly changing, must keep pace if be fully optimised. A symposium international experts was convened November 2022 explore current emerging issues identify opportunities approaches optimise care. This state-of-the-art review summarises key proceedings highlights priorities clinical practice research across lifespan among PWCF. It also initiatives intervention patient outcomes.

Language: Английский

---

Recent developments in cystic fibrosis drug discovery: where are we today?

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

The advent of variant-specific disease-modifying drugs into clinical practice has provided remarkable benefits for people with cystic fibrosis (PwCF), a multi-organ life-limiting inherited disease. However, further efforts are needed to maximize therapeutic as well increase the number PwCF taking CFTR modulators. authors discuss some key limitations currently available modulator therapies (e.g. adverse reactions) and strategies in development therapeutics CF. These include novel methods accelerate theratyping identification small molecules cellular targets representing alternative or complementary While CF therapy pipeline continues grow, there is critical need optimize that will testing approval effective (ultra)rare variants traditional assays trials not suitable address such issues. Another major barrier needs be solved restricted access therapies, which remains significant burden who from racial ethnic minorities living underprivileged regions.

Language: Английский

---

Severe mental health changes in patients with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor therapy

Pediatric Pulmonology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Due to the nature of research, due ethical restrictions, supporting data is not available.

Language: Английский

---

Improved Clinical Outcomes With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease: Real‐World Evidence From an Italian Single‐Center Study

Pharmacology Research & Perspectives, Journal Year: 2025, Volume and Issue: 13(2)

Published: April 1, 2025

The combination of Elexacaftor/Tezacaftor/Ivacaftor (ETI) has resulted in a significant improvement lung function and global clinical parameters, which have not been previously achieved with other CFTR modulators. However, there is paucity evidence the literature on long-term use ETI adolescents patients severe pulmonary impairment. Furthermore, response to may differ between homozygotes heterozygotes, as well naïve those treated A retrospective study was conducted examine changes percent predicted forced expiratory volume 1 s (ppFEV1), body-mass index (BMI), sweat chloride concentration (SwCl) at baseline 6, 12 24 months after initiation ETI. Secondary outcomes included number exacerbations, Cystic Fibrosis Questionnaire-Revised (CFQ-R) score, adverse events, mortality transplantation rates. 139 subjects were followed up for 2 years starting results demonstrated ppFEV1 BMI therapy (respectively, 16%, p < 0.001; +1.5 kg/m2, = 0.005), slight decline values months. This effect independent genotype showed different degree compared SwCl decreased from 84 37 mmol/L over (p 0.001). 58.3% reduction PEx rate observed exacerbations prior Overall, function, SwCl, rate, CFQ-R scores improved treatment. tolerated, none interrupted treatment due toxicity.

Language: Английский

---

Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases

Israel Journal of Chemistry, Journal Year: 2024, Volume and Issue: 64(12)

Published: Jan. 24, 2024

Abstract Cystic Fibrosis (CF) is a genetic disorder resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to faulty CFTR protein. Dysfunctional causes chloride ion imbalance, dense mucus accumulation various organs, particularly lungs. CF treatments focus on symptom management and addressing CFTR′s functional defects. Notably, development of modulator therapies has significantly advanced treatment. These drugs target protein structural defects induced by mutations, restoring its function improving symptoms. VX‐770, potentiator, correctors like VX‐809, VX‐661, VX‐445, have gained FDA approval widespread clinical use, greatly enhancing health survival many patients. However, some lack effective targeted therapies, leaving approximately 6 % patients without suitable options. proven essential for combating underlying misfolding diseases, serving as blueprint similar other membrane diseases. This review explores current future applications established paradigms Ongoing research innovation hold potential further improvements treatment

Language: Английский

---