CFTR modulator therapy alters plasma sphingolipid profiles in people with cystic fibrosis

Westhölter, Dirk; Schumacher, Fabian; Wülfinghoff, Nuria; Sutharsan, Sivagurunathan; Straßburg, Svenja; Kleuser, Burkhard; Horn, Peter A.; Reuter, Sebastian; Gulbins, Erich; Taube, Christian; Welsner, Matthias

doi:10.1016/j.jcf.2022.02.005

Cited by 13 publications

(15 citation statements)

References 34 publications

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“…As ceramidases the key enzymes in cell survival maintaining, their potential therapeutic role could be investigate 33 . Despite evidences, showing an increment of ceramides associated with the increased inflammation and grater susceptibility to infection in CF, Westholter et al 34 demonstrated a deficit of www.nature.com/scientificreports/ sphingosine and ceramides. However, the authors discuss about an imbalanced ceramides composition in blood from a large cohort of CF patients suggesting an alteration of specific ceramides subtypes rather than a general upregulation of ceramides in CF serum.…”

Section: Discussionmentioning

confidence: 97%

Lipidomic alterations in human saliva from cystic fibrosis patients

Caterino

Fedele

Carnovale

et al. 2023

Sci Rep

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Cystic fibrosis is a hereditary metabolic disorder characterized by impaired traffic of chloride ions and water through membranes of the respiratory and gastrointestinal, that causes inadequate hydration of airway surfaces, dehydrated mucous secretions and a high-sodium chloride sweat. Although the classical presentation of the condition is well known, a better characterization of metabolic alterations related is need. In particular, the metabolic composition alterations of biological fluids may be influence by the disease state and could be captured as putative signature to set targeted therapeutic strategies. A targeted comprehensive mass spectrometry-based platform was employed to dissect the lipid content of saliva samples form CF patients, in order to investigate alterations in the lipid metabolic homeostasis related to the pathology, chronic obstructive pulmonary disease, Pseudomonas Aeruginosa infection, pancreatic insufficiency, liver disfunction and diabetes-related complications.

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Section: Discussionmentioning

confidence: 97%

Lipidomic alterations in human saliva from cystic fibrosis patients

Caterino

Fedele

Carnovale

et al. 2023

Sci Rep

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“…Our results, as seen in Figures 6 and 7 corroborate their findings ( Figure 4 ), of a downregulation in C14:0 and C16:0 and a concomitant upregulation in VLCCs ( Liessi et al, 2020 ). Recently, an interesting study was published by Westholter and others reporting ceramide levels obtained from plasma analysis of 25 PwCF (age 35.56 ± 12.75; 20 out of 25 with intermittent or chronic Pseudomonas infection) treated for 4 weeks with TRIKAFTA® ( Westhölter et al, 2022 ). A very modest improvement (decrease) in C16:0 ceramide levels (0.218 ± 0.09 before treatment and 0.178 ± 0.06 ( p = 0.0051) after 4 weeks of treatment) with TRIKAFTA® was reached.…”

Section: Discussionmentioning

confidence: 99%

“…No improvement in C22:0 or C24:1 ceramide was reported following the treatment with TRIKAFTA® and no analysis of C26:0 ceramides was done. The ratio between C16Cer/C24Cer has improved from 0.171 ± 0.06 before treatment to 0.112 ± 0.03 after 4 weeks of TRIKAFTA® treatment ( p -value = <0.001) ( Westhölter et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease

et al. 2022

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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.

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“…Sphingolipids -bioactive structural components of cell membranes -appear dysregulated in people with cystic fibrosis. Through liquid chromatography mass spectrometry analysis of plasma from people with cystic fibrosis pre-and 1 month post-ETI treatment, Dirk Westhölter (Ruhrlandklinik, Germany) found that ETI treatment alters plasma sphingolipid profiles towards a favourable outcome (68).…”

Section: Session: Advances In Cystic Fibrosis Researchmentioning

confidence: 99%

ERS International Congress 2022: highlights from the Respiratory Infections Assembly

Banka

Chichirelo-Konstantynovych

Horton

et al. 2023

ERJ Open Res

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The European Respiratory Society Annual Congress took place both in-person, in Barcelona, Spain, and online in 2022. The congress welcomed over 19,000 attendees on this hybrid platform, bringing together exciting updates in respiratory science and medicine from around the world. In this article, Early Career Members of the Respiratory Infections Assembly 10 summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, non-tuberculosis mycobacteria, tuberculosis, cystic fibrosis and COVID-19.

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CFTR modulator therapy alters plasma sphingolipid profiles in people with cystic fibrosis

Cited by 13 publications

References 34 publications

Lipidomic alterations in human saliva from cystic fibrosis patients

Lipidomic alterations in human saliva from cystic fibrosis patients

Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease

ERS International Congress 2022: highlights from the Respiratory Infections Assembly

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