Project description
Gene therapy for congenital heart block
The rhythmic pumping function of the heart muscle is mediated by a built-in electrical system. In congenital complete heart block (CCHB) this system malfunctions due to structural defects or autoimmunity, causing abnormal propagation of electrical impulses in the heart. CCHB is diagnosed in utero, at birth or during the first months of life and is associated with bradycardia. The only treatment is the implantation of a permanent pacemaker. The ERC-based RescuePace project proposes a gene therapy approach to treat CCHB. The procedure entails the administration of an adenoviral vector that expresses ion channels in the heart to increase the heart rate and allow the patient to survive until birth, when a pacemaker can be implanted.
Objective
Congenital heart block is the most commonly observed type of foetal bradycardia, occurring in one in 15.000 live births. A significant subset of foetuses develops towards congenital complete heart block (CCHB), i.e. complete failure of the electrical excitation wavefront to be conducted over the atrioventricular (AV) node. CCHB is the most severe and life-threatening cardiac arrhythmia in utero. Current medicinal treatments cannot significantly alter the cause of CCHB and therapeutic attempts at human foetal cardiac pacing have been unsuccessful. For CCHB patients at high risk for life-threatening disease progression and death due to severe bradycardia before 34 weeks of gestation, this project develops a gene therapy medicinal product (GTMP) that is based on adenoviral vector-mediated ion channel overexpression, to transiently increase heart rates over the course of several months. When successful, such a GTMP would rescue these patients and allow for permanent pacemaker implantation in the first months after birth.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC-POC - HORIZON ERC Proof of Concept GrantsHost institution
1081 HV Amsterdam
Netherlands