Related Experiment Video

Updated: Apr 4, 2026

Expression and Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein in Saccharomyces cerevisiae
14:56

Expression and Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein in Saccharomyces cerevisiae

Published on: March 10, 2012

19.2K

Systemic effects of cystic fibrosis transmembrane conductance regulator modulators on the plasma and serum proteome

Kerstin Fentker1, Marieluise Kirchner2, Matthias Ziehm2

  • 1Proteomics Platform, Max Delbrück Center for Molecular Medicine, Berlin, Germany; Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.

Cell Systems
|April 3, 2026
PubMed

Insights

New CFTR modulator drugs show broader systemic benefits for cystic fibrosis patients. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) therapy normalizes protein profiles more effectively than lumacaftor/ivacaftor (LUM/IVA).

Area of Science:

  • Biochemistry and Molecular Biology
  • Medical Genetics and Genomics
  • Pulmonology and Respiratory Medicine

Background:

  • Cystic fibrosis (CF) is a multi-organ genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
  • CFTR modulator therapies have improved clinical outcomes but their systemic molecular effects require further investigation.

Purpose of the Study:

  • To compare the plasma and serum proteomic changes in cystic fibrosis patients treated with dual (lumacaftor/ivacaftor) versus triple (elexacaftor/tezacaftor/ivacaftor) CFTR modulator therapy.
  • To elucidate the broader molecular and systemic effects of different CFTR modulator regimens.

Main Methods:

  • Mass-spectrometry-based proteomics was utilized to analyze plasma and serum samples.
  • Proteomic profiles of patients receiving lumacaftor/ivacaftor (LUM/IVA) were compared with those receiving elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA).

Main Results:

  • Both CFTR modulator regimens showed distinct and overlapping proteomic signatures related to inflammation and metabolic processes.
  • The triple combination therapy (ELX/TEZ/IVA) demonstrated more consistent effects, aligning protein profiles closer to those of healthy individuals.
  • ELX/TEZ/IVA therapy resulted in broader improvements in protein dysregulation compared to LUM/IVA.

Conclusions:

  • Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) therapy offers more comprehensive systemic benefits in cystic fibrosis patients than lumacaftor/ivacaftor (LUM/IVA).
  • Observed proteomic changes provide insights into the systemic impact of CFTR modulators and may guide future therapeutic strategies for cystic fibrosis.
Keywords:
AstralCFTR modulatorDIAELX/TEZ/IVALUM/IVAcystic fibrosishumanmass spectrometryplasmaproteomicsserumsputum

More Related Videos

Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein Expressed in Saccharomyces cerevisiae15:12

Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein Expressed in Saccharomyces cerevisiae

Published on: May 10, 2014

15.1K
Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study08:00

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study

Published on: April 11, 2018

11.2K

Related Concept Videos

Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
1.1K
Cystic Fibrosis: Management01:24

Cystic Fibrosis: Management

Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...
620
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
112
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
901
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
44.6K