Summary
The Arora lab at Northwestern University proposes to investigate the fundamental molecular mechanisms underlying the progression of atrial fibrillation (AF) from paroxysmal to persistent forms, focusing on structural changes and developing novel gene therapy approaches, including an electroporation-based delivery method.
What they want
The project aims to obtain a better understanding of the molecular mechanisms that underlie the progression of paroxysmal AF to persistent AF. This includes studying structural changes such as new parasympathetic nerve sprouting, NLRP3 inflammasome mediated fibrosis, and HDAC6 mediated breakdown of microtubules (derailed proteastasis). These mechanisms will be studied in chronically tachypaced large animal models of AF using novel gene therapy approaches developed in the lab. A major goal is also to fully develop and optimize a highly novel electroporation-based approach to facilitate trans-venous gene delivery, with the ultimate goal of developing a clinically viable gene therapy for persistent AF.
Deliverables
- Fresh mechanistic insights into the creation of an atrial myopathy that supports persistent AF
- Development of new, potentially paradigm-shifting therapeutic approaches to AF
- Demonstration of therapeutic potential of gene therapy approaches in arresting progression of paroxysmal AF to persistent AF
- Fully developed and optimized electroporation-based gene delivery approach
- Identification of novel gene therapy targets for AF
Technical requirements
- Use of chronically tachypaced large animal models of AF
- Application of novel gene therapy approaches developed in the Arora lab
- Development and optimization of an electroporation-based approach for trans-venous gene delivery
Risks & flags
Incumbent: Arora lab at Northwestern University
