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Role of Anti-TREK-1 Autoantibodies in SCVF
Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Summary
Short-coupled ventricular fibrillation (SCVF) is a lethal, primary electrical disorder and an important cause of unexplained cardiac arrest.1 Recent work from our group suggests that a substantial proportion of SCVF cases is associated to circulating autoantibodies targeting TREK-1, a cardiac potassium channel, resulting in an abnormal gain-of-function which is the prerequisite for the SCVF phenotype.2 This proposal is a translational multicenter study to validate anti-TREK-1 autoantibodies as a diagnostic and prognostic biomarker in a large, diversified cohort of SCVF patients (Figure 1). Functional, cellular experiments in patient-derived hiPSC cardiomyocytes and Purkinje cells will be performed to explore the cell type-specific role of TREK-1 in arrhythmogenesis, while single-nuclear RNA sequencing (snRNA-seq) will allow us to establish the transcriptomic profile (Figure 1). These results will identify the cellular substrate for SCVF.
Official title: Circulating Anti-TREK-1 Autoantibodies as Diagnostic and Prognostic Biomarkers in Short-Coupled Ventricular Fibrillation
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
OBSERVATIONAL
Enrollment
300
Start Date
2025-05-01
Completion Date
2028-12-31
Last Updated
2025-04-24
Healthy Volunteers
No
Interventions
Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies
Semiquantitative measure of circulating anti-TREK-1 autoantibodies in plasma of study participants using a peptid microarray
DPP6 risk haplotype
Systematic genetic screening for the Dutch DPP6 risk haplotype in all study participants and correlation of results with the presence or absence of anti-TREK-1 autoantibodies
Locations (1)
Institut universitaire de cardiologie et pneumologie de Québec
Québec, Quebec, Canada