Cystic fibrosis: Toward personalized therapies
| Autor: | Marcel J. C. Bijvelds, Pauline T. Ikpa, Hugo R. de Jonge |
|---|---|
| Přispěvatelé: | Gastroenterology & Hepatology |
| Rok vydání: | 2014 |
| Předmět: |
Cystic Fibrosis
business.industry medicine.medical_treatment Cystic Fibrosis Transmembrane Conductance Regulator Nanotechnology Cell Biology Stem-cell therapy Disease Genetic Therapy Potentiator Bioinformatics medicine.disease Biochemistry Cystic fibrosis SDG 3 - Good Health and Well-being medicine Chloride channel Organoid Humans Personalized medicine Precision Medicine business Ex vivo |
| Zdroj: | International Journal of Biochemistry & Cell Biology, 52, 192-200. Elsevier Ltd. |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2014.02.008 |
| Popis: | Cystic fibrosis (CF), the most common, life-threatening monogenetic disease in Caucasians, is caused by mutations in the CFTR gene, encoding a cAMP- and cGMP-regulated epithelial chloride channel. Symptomatic therapies treating end-organ manifestations have increased the life expectancy of CF patients toward a mean of 40 years. The recent development of CFTR-targeted drugs that emerged from high-throughput screening and are capable of correcting the basic defect promises to transform the therapeutic landscape from a trial-and-error prescription to personalized medicine. This stratified approach is tailored to a specific functional class of mutations in CFTR, but can be refined further to an individual level by exploiting recent advances in ex vivo drug testing methods. These tests range from CFTR functional measurements in rectal biopsies donated by a CF patient to the use of patient-derived intestinal or pulmonary organoids. Such organoids may serve as an inexhaustible source of epithelial cells that can be stored in biobanks and allow medium- to high-throughput screening of CFTR activators, correctors and potentiators on the basis of a simple microscopic assay monitoring organoid swelling. Thus the recent breakthrough in stem cell biology allowing the culturing of mini-organs from individual patients is not only relevant for future stem cell therapy, but may also allow the preclinical testing of new drugs or combinations that are optimally suited for an individual patient. (C) 2014 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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