Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a inherited arrhythmia syndrome characterized by life-threatening arrhythmias during times of stress or exercise.Dominant mutations in the intracellular calcium (Ca2+) release channel RYR2 are responsible for the majority of clinical cases. Despite maximal medical therapy, patients continue to have breakthrough events or therapy related complications. To response to this unmet clinical need, we have developed a targeted gene therapy to suppress arrhythmias by inhibiting the Ca2+ regulated kinase CaMKII. Using adeno-associated virus (AAV) vectors we demonstrated efficacy in cellular and animal models of CPVT by targeted expression of CaMKII peptide inhibitors. This grant proposal is focused on the further refinement and testing of a clinical CaMKII peptide inhibitory vector in preparation for a human clinical trial.During this granting period we have determined the cardiac-specific promoter for optimal transgene expression and laid the foundation for refinement of the peptide inhibitor. We have also expanded our clinical network of CPVT patients and performed analysis of current healthcare costs for CPVT management.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1199615
Entities
People
- William T. Pu