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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
2026-06-16
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 (5)
St-Paul's Hospital - University of British Columbia
Vancouver, British Columbia, Canada
PHRI
Hamilton, Ontario, Canada
Ottawa Heart Center
Ottawa, Ontario, Canada
Institut universitaire de cardiologie et pneumologie de Québec
Québec, Quebec, Canada
Amsterdam University Medical Center
Amsterdam, Netherlands