Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia

Abstract

CPVT (Catecholaminergic Polymorphic Ventricular Tachycardia) is a dangerous form of congenital heart disease that puts patients at risk for lethal arrhythmias, especially during exercise or emotional stress. We have developed a viral vector that protects mouse models of CPVT and human CPVT patient stem cell-derived cardiomyocytes from developing arrhythmias. Our objective is to develop this viral vector into a new CPVT treatment. Our development plan is to optimize the treatment vector and then identify the effective dose in the CPVT mouse model. We will then perform safety studies in a large animal (swine). Finally, we will lay the foundation for a clinical trial by establishing a CPVT Network and establishing baseline data for patients under current standard-of-care therapy, and by submitting a US Food and Drug Administration (FDA) Investigational New Drug (IND) application. This proposal is relevant to the Peer Reviewed Medical Research Program (PRMRP) Topic Area of Congenital Heart Disease, since it will develop a new treatment for CPVT, a type of congenital heart disease. The proposal is also relevant to the PRMRP Topic Area of Cardiomyopathy (heart muscle weakness). Based on its mechanism of action, we anticipate that our therapy vector will be beneficial for both inherited and acquired forms of cardiomyopathy. Both congenital heart disease and cardiomyopathy are “Areas of Encouragement” within the PRMRP Topic Areas. This study will impact patients with CPVT. No approved gene therapies exist for heart disease, so this study may have impacts beyond this diagnosis by inspiring development of other gene therapy strategies. Moreover, because the mechanism of action is predicted to be beneficial in many forms of heart disease, this therapy may have a much broader impact in other forms of inherited heart disease, as well as acquired heart disease that is common among older patients, including Veterans.

Document Details

Document Type
DoD Grant Award
Publication Date
Nov 19, 2019
Source ID
W81XWH1910473

Entities

People

  • William T. Pu

Organizations

  • Boston Children's Hospital
  • United States Army

Tags

Fields of Study

  • Medicine

Readers

  • Cardiovascular Physiology
  • Infectious Disease/Epidemiology
  • Neurotrauma and Rehabilitation Medicine.

Technology Areas

  • Biotechnology