Jan 1, 2013

Novel opportunities for CFTR-targeting drug development using organoids

Rare Diseases
Johanna F DekkersJeffrey M Beekman

Abstract

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR mutations lead to production of non-functional CFTR, reduced amounts of normal functioning CFTR or misfolded CFTR with defects in trafficking or function. For decades, CF treatment has been focused on the symptoms of CF, but pharmacotherapy using small molecules that target the basic defect of CF, the mutant CFTR protein, is now possible for a limited amount of subjects with CF. This raises the exciting possibility that the majority of people with CF may receive effective treatment targeting the different CFTR mutants in the future. We recently described a functional CFTR assay using rectal biopsies from subjects with CF that were cultured in vitro into self-organizing mini-guts or organoids. We here describe how this model may assist in the discovery of new CFTR-targeting drugs, the subjects that may benefit from these drugs, and the mechanisms underlying variability in CFTR genotype-phenotype relations.

  • References30
  • Citations23

Citations

Mentioned in this Paper

Drug Development
Cystic Fibrosis
Thyroid Hormone Plasma Membrane Transport Defect
Trafficking
Etiology
CFTR gene
Mutant
Cytochrome p450 CYP4A11 Enzyme Activity
Biopsy
Cystic Fibrosis Transmembrane Conductance Regulator

Related Feeds

CFTR Mutant Structural Therapy

Over 1700 different mutations in the CFTR genes have been shown to cause cystic fibrosis. Here is the latest research on structural therapy for CFTR mutants.

Related Papers

Clinics and Research in Hepatology and Gastroenterology
S Erlinger
The New England Journal of Medicine
Michael J HarrisonBarry J Plant
The International Journal of Biochemistry & Cell Biology
Pauline T IkpaHugo R de Jonge
© 2020 Meta ULC. All rights reserved