BACKGROUND: Eluforsen is an antisense oligonucleotide designed to bind to the mRNA region around the F508-encoding deletion and restore the cystic fibrosis transmembrane conductance regulator (CFTR) protein function in the airway epithelium. We assessed the safety and tolerability, pharmacokinetics and exploratory measures of efficacy of inhaled eluforsen in cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. METHODS: This randomised, double-blind, placebo-controlled, dose escalation 1b study recruited adult CF subjects with a FEV1 > 70% predicted in four single ascending dose cohorts and four multiple ascending dose cohorts. Primary objectives were safety and tolerability. Secondary endpoints included pharmacokinetics, percent predicted forced expiratory volume in 1 s (ppFEV1), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Symptom Score (RSS). RESULTS: Single and multiple doses of inhaled eluforsen up to 50 mg were safe and well tolerated. A maximum tolerated dose was not established. Systemic exposure was low in all cohorts and lung function remained stable throughout the study. Three of four eluforsen-treated groups in the MAD study demonstrated an improvement in CFQ-R RSS at end of treatment with adjusted mean change from baseline values ranging from 6.4 to 12.7 points. In comparison, there was a mean decrease of 6.5 points in the placebo group from baseline to end of treatment. CONCLUSIONS: Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients.

• Klíčová slova
• Antisense oligonucleotide, CFQ-R RSS, Clinical trial, Delta F508, Pulmonary medicine,
• MeSH
• antisense oligonukleotidy aplikace a dávkování   škodlivé účinky   MeSH
• aplikace inhalační MeSH
• cystická fibróza * farmakoterapie   genetika   patofyziologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• klinické křížové studie MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• mutace MeSH
• oligonukleotidy * aplikace a dávkování   škodlivé účinky   MeSH
• protein CFTR genetika   MeSH
• respirační funkční testy metody   MeSH
• určení symptomu metody   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antisense oligonukleotidy MeSH
• CFTR protein, human MeSH Prohlížeč
• eluforsen MeSH Prohlížeč
• oligonukleotidy * MeSH
• protein CFTR MeSH

• Klíčová slova
• Cystic fibrosis, Elexacaftor/tezacaftor/ivacaftor, Exocrine pancreatic insufficiency,
• MeSH
• aktivátory chloridových kanálů terapeutické užití   MeSH
• aminofenoly * terapeutické užití   MeSH
• benzodioxoly * terapeutické užití   MeSH
• chinoliny terapeutické užití   MeSH
• chinolony * terapeutické užití   MeSH
• cystická fibróza * farmakoterapie   genetika   MeSH
• dospělí MeSH
• exokrinní pankreatická insuficience farmakoterapie   etiologie   genetika   MeSH
• fixní kombinace léků MeSH
• genotyp MeSH
• indoly * terapeutické užití   MeSH
• lidé MeSH
• protein CFTR * genetika   MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• pyrrolidiny terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• Názvy látek
• aktivátory chloridových kanálů MeSH
• aminofenoly * MeSH
• benzodioxoly * MeSH
• chinoliny MeSH
• chinolony * MeSH
• elexacaftor, ivacaftor, tezacaftor drug combination MeSH Prohlížeč
• elexacaftor MeSH Prohlížeč
• fixní kombinace léků MeSH
• indoly * MeSH
• ivacaftor MeSH Prohlížeč
• protein CFTR * MeSH
• pyrazoly * MeSH
• pyridiny MeSH
• pyrrolidiny MeSH
• tezacaftor MeSH Prohlížeč

BACKGROUND: Several treatment approaches in cystic fibrosis (CF) aim to correct CF transmembrane conductance regulator (CFTR) function; the efficacy of each approach is dependent on the mutation(s) present. A need remains for more effective treatments to correct functional deficits caused by the F508del mutation. METHODS: Two placebo-controlled, phase 2a studies evaluated GLPG2222, given orally once daily for 29 days, in subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS). The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms. RESULTS: Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6 mmol/L [GLPG2222 200 mg], p < 0.0001; ALBATROSS: -7.4 mmol/L [GLPG2222 300 mg], p < 0.05). No significant effects on pulmonary function or respiratory symptoms were reported. Plasma GLPG2222 concentrations in CF subjects were consistent with previous studies in healthy volunteers and CF subjects. CONCLUSIONS: GLPG2222 was well tolerated. Sweat chloride reductions support on-target enhancement of CFTR activity in subjects with F508del mutation(s). Significant improvements in clinical endpoints were not demonstrated. Observed safety results support further evaluation of GLPG2222, including in combination with other CFTR modulators. FUNDING: Galapagos NV. Clinical trial registration numbers FLAMINGO, NCT03119649; ALBATROSS, NCT03045523.

• Klíčová slova
• CFTR modulator, Cystic fibrosis, F508del, GLPG2222, Gating mutation, Ivacaftor,
• MeSH
• aktivátory chloridových kanálů aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• aminofenoly * aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• benzoáty * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• benzopyrany * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• biologická dostupnost MeSH
• chinolony * aplikace a dávkování   škodlivé účinky   MeSH
• cystická fibróza * diagnóza   farmakoterapie   genetika   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• mutace MeSH
• pot * chemie   účinky léků   MeSH
• protein CFTR genetika   MeSH
• respirační funkční testy metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• aktivátory chloridových kanálů MeSH
• aminofenoly * MeSH
• benzoáty * MeSH
• benzopyrany * MeSH
• chinolony * MeSH
• GLPG2222 MeSH Prohlížeč
• ivacaftor MeSH Prohlížeč
• protein CFTR MeSH

BACKGROUND: On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. METHODS: We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. RESULTS: Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9x greater than VV subjects when F508del is excluded and 15.4x when F508del is included. In the Czech population a similar, although less pronounced, association is observed. CONCLUSIONS: Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.

• MeSH
• běloši genetika   MeSH
• cystická fibróza etnologie   genetika   MeSH
• frekvence genu genetika   MeSH
• genetické testování metody   MeSH
• heterozygot MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• pilotní projekty MeSH
• protein CFTR genetika   MeSH
• riziko MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika etnologie   MeSH
• Itálie etnologie   MeSH
• Názvy látek
• CFTR protein, human MeSH Prohlížeč
• protein CFTR MeSH

The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3'-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.

• Klíčová slova
• Cystic fibrosis, Differential expression, Elexacaftor, Intestinal organoid, Ivacaftor, Tezacaftor,
• MeSH
• aktivátory chloridových kanálů farmakologie   MeSH
• aminofenoly * farmakologie   MeSH
• benzodioxoly * farmakologie   MeSH
• chinoliny MeSH
• chinolony * farmakologie   MeSH
• cystická fibróza * genetika   farmakoterapie   MeSH
• fixní kombinace léků MeSH
• indoly * farmakologie   MeSH
• lidé MeSH
• organoidy * účinky léků   metabolismus   MeSH
• protein CFTR genetika   MeSH
• pyrazoly MeSH
• pyridiny * farmakologie   MeSH
• pyrrolidiny MeSH
• pyrroly * farmakologie   MeSH
• stanovení celkové genové exprese MeSH
• thiofeny farmakologie   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktivátory chloridových kanálů MeSH
• aminofenoly * MeSH
• benzodioxoly * MeSH
• chinoliny MeSH
• chinolony * MeSH
• elexacaftor, ivacaftor, tezacaftor drug combination MeSH Prohlížeč
• elexacaftor MeSH Prohlížeč
• fixní kombinace léků MeSH
• indoly * MeSH
• ivacaftor MeSH Prohlížeč
• protein CFTR MeSH
• pyrazoly MeSH
• pyridiny * MeSH
• pyrrolidiny MeSH
• pyrroly * MeSH
• tezacaftor MeSH Prohlížeč
• thiofeny MeSH

Decreased human epididymis protein 4 (HE4) plasma levels were reported in cystic fibrosis (CF) patients under CFTR potentiator ivacaftor therapy, which inversely correlated with lung function improvement. In this study, we investigated whether HE4 expression was affected via modulation of CFTR function in CF bronchial epithelial (CFBE) cells in vitro. HE4 protein levels were measured in the supernatants of CFBE 41o- cells expressing F508del-CFTR or wild-type CFTR (wt-CFTR) after administration of lumacaftor/ivacaftor or tezacaftor/ivacaftor, while HE4 expression in CFBE 41o- cells were also analyzed following application of adenylate cyclase activators Forskolin/IBMX or CFTRinh172. The effect of all of these compounds on CFTR function was monitored by the whole-cell patch-clamp technique. Induced HE4 expression was studied with interleukin-6 (IL-6) in F508del-CFTR CFBE 41o- cells under TNF-α stimulation for 1 h up to 1 week in duration. In parallel, plasma HE4 was determined in CF subjects homozygous for p.Phe508del-CFTR mutation receiving lumacaftor/ivacaftor (Orkambi®) therapy. NF-κB-mediated signaling was observed via the nuclear translocation of p65 subunit by fluorescence microscopy together with the analysis of IL-6 expression by an immunoassay. In addition, HE4 expression was examined after NF-κB pathway inhibitor BAY 11-7082 treatment with or without CFTR modulators. CFTR modulators partially restored the activity of F508del-CFTR and reduced HE4 concentration was found in F508del-CFTR CFBE 41o- cells that was close to what we observed in CFBE 41o- cells with wt-CFTR. These data were in agreement with decreased plasma HE4 concentrations in CF patients treated with Orkambi®. Furthermore, CFTR inhibitor induced elevated HE4 levels, while CFTR activator Forskolin/IBMX downregulated HE4 in the cell cultures and these effects were more pronounced in the presence of CFTR modulators. Higher activation level of baseline and TNF-α stimulated NF-κB pathway was detected in F508del-CFTR vs. wt-CFTR CFBE 41o- cells that was substantially reduced by CFTR modulators based on lower p65 nuclear positivity and IL-6 levels. Finally, HE4 expression was upregulated by TNF-α with elevated IL-6, and both protein levels were suppressed by combined administration of NF-κB pathway inhibitor and CFTR modulators in CFBE 41o- cells. In conclusion, CFTR dysfunction contributes to abnormal HE4 expression via NF-κB in CF.

• Klíčová slova
• CFTR modulator, HE4, bronchial epithelial cell, cystic fibrosis, inflammation,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: For most of the >2000 CFTR gene variants reported, neither the associated disease liability nor the underlying basic defect are known, and yet these are essential for disease prognosis and CFTR-based therapeutics. Here we aimed to characterize two ultra-rare mutations - 1717-2A > G (c.1585-2A > G) and S955P (p.Ser955Pro) - as case studies for personalized medicine. METHODS: Patient-derived rectal biopsies and intestinal organoids from two individuals with each of these mutations and F508del (p.Phe508del) in the other allele were used to assess CFTR function, response to modulators and RNA splicing pattern. In parallel, we used cellular models to further characterize S955P independently of F508del and to assess its response to CFTR modulators. RESULTS: Results in both rectal biopsies and intestinal organoids from both patients evidence residual CFTR function. Further characterization shows that 1717-2A > G leads to alternative splicing generating <1% normal CFTR mRNA and that S955P affects CFTR gating. Finally, studies in organoids predict that both patients are responders to VX-770 alone and even more to VX-770 combined with VX-809 or VX-661, although to different levels. CONCLUSION: This study demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs to patients with rare mutations.

• Klíčová slova
• CFTR modulators, Intestinal organoids, Precision medicine, Rare mutations, Theranostics,
• MeSH
• alely MeSH
• aminofenoly terapeutické užití   MeSH
• aminopyridiny terapeutické užití   MeSH
• benzodioxoly terapeutické užití   MeSH
• chinolony terapeutické užití   MeSH
• cystická fibróza farmakoterapie   genetika   MeSH
• elektrofyziologie MeSH
• fluorescenční protilátková technika MeSH
• genotyp MeSH
• individualizovaná medicína metody   MeSH
• indoly terapeutické užití   MeSH
• lidé MeSH
• mutace genetika   MeSH
• protein CFTR genetika   metabolismus   MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminofenoly MeSH
• aminopyridiny MeSH
• benzodioxoly MeSH
• chinolony MeSH
• indoly MeSH
• ivacaftor MeSH Prohlížeč
• lumacaftor MeSH Prohlížeč
• protein CFTR MeSH
• tezacaftor MeSH Prohlížeč

OBJECTIVE: The presentation of the results of molecular genetics analysis in men with reproductive disorders and in gamete donors with a focus on interpretation of the results CFTR gene analysis. DESIGN: Original article. SETTING: Institute of Biology and Medical Genetics of the First Faculty of Medicine and General Teaching Hospital. METHODS: We examined 164 men with reproductive disorders for 36 selected mutations in CFTR gene including T(n) polymorphism and for Y chromosome microdeletions. As well we examined mutations in CFTR gene including T(n) polymorphism in 104 gamete donors. RESULTS: We detected microdeletions in AZF region in 3 cases of affected men and in other 3 casses we found mutation F508del (heterozygotes) in CFTR gene with T5 variant in trans position. Except this we detected in 5 affected men "only" heterozygous mutations in CFTR gene and in 12 men "only" the T5 variant in heterozygous level. Among gamete donors we found 3 heterozygotes for mutation F508del and 11 heterozygotes for T5 variant. CONCLUSION: In infertile men and in gamete donors we recommend to examine not only the "classical" mutations in CFTR gene but also the relatively frequent T5 variant, which can be in certain conditions considered as a pathogenic mutation. It's necessary to rule out the carriers of T5 variation from gamete donors.

• MeSH
• dárci tkání * MeSH
• genetické lokusy MeSH
• heterozygot MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• mužská infertilita genetika   MeSH
• polymorfismus genetický * MeSH
• protein CFTR genetika   MeSH
• proteiny semenné plazmy genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• protein CFTR MeSH
• proteiny semenné plazmy MeSH

BACKGROUND: Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. METHODS: Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. RESULTS: Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. CONCLUSIONS: HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

• Klíčová slova
• CFTR mutations, CRP, FEV(1), HE4, cystic fibrosis, inflammation, sweat test,
• MeSH
• bronchiální astma genetika   metabolismus   MeSH
• bronchiektazie genetika   metabolismus   MeSH
• bronchitida genetika   metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• cystická fibróza genetika   metabolismus   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• epitelové buňky metabolismus   MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mikro RNA metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pneumonie genetika   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• předškolní dítě MeSH
• protein CFTR genetika   MeSH
• protein WFDC2 MeSH
• proteiny genetika   metabolismus   MeSH
• respirační sliznice metabolismus   MeSH
• spirometrie MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• usilovný výdechový objem MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• CFTR protein, human MeSH Prohlížeč
• messenger RNA MeSH
• mikro RNA MeSH
• Mirn140 microRNA, human MeSH Prohlížeč
• protein CFTR MeSH
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.

• Klíčová slova
• LAU-7b, TRIKAFTA, ceramides, cystic fibrosis, fenretinide (4-HPR), lung physiology, sphingolipids, triple therapy,
• Publikační typ
• časopisecké články MeSH