HPSCLQT
Human pluripotent stem cells for modeling and correcting long-QT syndrome
| Coordinatore | ACADEMISCH ZIEKENHUIS LEIDEN
Organization address
address: Albinusdreef 2 contact info |
| Nazionalità Coordinatore | Netherlands [NL] |
| Totale costo | 183˙805 € |
| EC contributo | 183˙805 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2011-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2012 |
| Periodo (anno-mese-giorno) | 2012-05-01 - 2014-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
ACADEMISCH ZIEKENHUIS LEIDEN
Organization address
address: Albinusdreef 2 contact info |
NL (LEIDEN) | coordinator | 183˙805.80 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (Objective)
'The long QT syndrome (LQTS) is an inherited or acquired disorder characterized by delayed ventricular repolarization predisposing affected individuals to fatal cardiac arrhythmias. In ~90% of the familial cases, LQTS is associated with mutation in two potassium voltage-gated channel genes: KCNQ1, causing LQT1, and KCNH2, causing LQT2. Since the first report of human induced pluripotent stem cells (hiPSC), lines have been obtained from patients with both genetic and sporadic diseases. LQT1- and LQT2-hiPSC recapitulate the disease phenotype and they have been used to understand the underlying molecular mechanisms. The aims of this project are 1) to correct LQT1- and LQT2-causing mutations in patient-specific hiPSC; 2) to target the same nucleotide changes in human embryonic stem cells (hESC); 3) to characterize the electrophysiological phenotype of cardiomyocytes derived from “genetically corrected” patient-specific iPSCs and from mutated hESCs; and 4) to compare the pharmacological response of derivative cardiomyocytes. Gene targeting in hiPSC and in hESC will be performed using conventional homologous recombination techniques. Correcting the mutation in hiPSC will allow us to assess whether the mutation is causally linked to the electrophysiological phenotype. By targeting the same mutations in hESC, causality of the individual genetic defects will be confirmed and model systems of LQT1 and LQT2 will be generated (panel of diverse single mutations in one genetic background). We will also determine whether the mutations increase drug sensitivity thereby enhancing arrhythmogenic risk. Myocytes harboring LQTS-associated mutation will provide a crucial tool to screen drug compounds for the future development of pharmacological therapy.'
Introduzione (Teaser)
Patient-derived human induced pluripotent stem cells (hiPSCs) offer unique opportunities to study molecular dynamics and drug pharmacology. Important understanding related to a genetic heart condition predisposing patients to arrhythmias has been obtained using hiPSCs.