NaV 1.5 regulation fine-tuning as a therapy
for cardiac Conduction and Arrhythmic diseases at Risk of suddEn Death
About NaV1.5-CARED, a European research program
The NaV1.5-CARED project is a research program funded by the EIC Pathfinder Challenge "Cardiogenomics" programme to identify and develop innovative therapies for patients at risks of sudden cardiac death.
The voltage-gated sodium channel (Na-channel, NaV 1.5) is a central component of cardiac electrogenesis. Its dysfunction can lead to ventricular fibrillation and sudden cardiac death.
While NaV 1.5 represents a highly relevant therapeutic target for prevention of life-threatening cardiac arrhythmias, therapies that target the expression or function of this channel are non-existent. Such a therapy would provide for the first time an alternative for the invasive and costly cardioverter defibrillator or pacemaker therapies currently used to treat patients suffering from a Brugada syndrome and/or a progressive cardiac conduction disease.
NaV1.5-CARED consortium proposes to capitalize on their largest worldwide cohorts of patients with inherited cardiac electrical disorders to conduct genetics studies and uncover regulatory regions and proteins that modulate NaV1.5 expression and function.
Our goal is to develop and validate innovative therapies to restore the function of NaV1.5.
4 Objectives:
1
Stratify the risk of (fatal) cardiac arrhythmia and conduction defect at the individual level
by developing personalized polygenic risk score (PRS)
2
Identify genomic region regulating sodium-channel gene expression
3
Develop cellular models to evaluate the efficiency of new therapeutic tools at restoring the NaV1.5 loss of function
4
Evaluate through pre-clinical tests new candidates for therapeutic intervention