Transcriptional targeting of pacemaker and conduction system gene therapy

Title Transcriptional targeting of pacemaker and conduction system gene therapy
Acronym PACE
Start date 2020-01-01
End date 2023-01-01
Sponsor European Research Council - Proof of Concept (ERC-PoC)
Institution University of Amsterdam - Academic Medical Center

Associated cell lines

Project Description

The problem: Ageing and age-related diseases cause degeneration of the cardiac conduction system (CCS) that creates and conducts the electrical impulse which drives the heart beat (pacing). The resulting slow heart rate (bradycardia) necessitates electronic pacemaker implantation in 500,000 patients yearly in Europe (direct costs of €3.4 billion). This current state-of-the-art treatment has significant limitations (dangerous complications, reduced quality-of-life) that, stemming from its design, may never be resolved. Regeneration of CCS function is conceptually superior and scientific discoveries, enabling CCS regeneration, were recently made. Closest to clinical testing are a variety of gene therapy-based strategies that can provide for biological pacing. Complementary strategies to repair conduction are also under development. The solution: To transit biological pacemaker therapies towards clinical testing it will be crucially important to optimize the gene delivery vectors with transcriptional targeting to the CCS. This will provide for more efficient and safer vectors that can be utilized in the context of biological pacing and repair of compromised conduction. The PACE project is designed to provide for final proof-ofconcept in the development path, moving forward from scientific discovery towards clinical implementation and testing. As such the PACE project will optimize and validate the use of CCS-specific cis-acting regulatory modules (CRMs) to optimize transcriptional targeting to desired CCS components in the heart and validate these in vivo. The development and validation of these CCS-targeted vectors will importantly strengthen our IP-position, thereby supporting the business development efforts that are an integral part of the PACE project