Evidence map›Paper›PMID 31155924›Full record

ArticleCirculation2019

Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca

Vassilios J Bezzerides, Ana Caballero, Suya Wang, Yulan Ai, Robyn J Hylind, Fujian Lu, Danielle A Heims-Waldron, Kristina D Chambers, Donghui Zhang, Dominic J Abrams and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 142 citations in OpenAlex.

  1. An RYR2-interacting fragment of MYBPC3 mitigates arrhythmia in human iPSC-CM and mouse models of CPVT.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. Article
  3. Review
  4. Ca2+ signalling in cardiac muscle: the importance of balances.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Genes & diseases · 2026
    Review
  9. Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026
    Review
  10. Review
  11. Gene Therapy for Inherited Cardiac Arrhythmias.Journal of cardiovascular translational research · 2025
    Review
  12. Review
  13. Article
  14. Review
  15. Role of Dyadic Proteins in Proper Heart Function and Disease.International journal of molecular sciences · 2025
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Extracellular Kir2.1Circulation research · 2024
    Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Vassilios J BezzeridesBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Ana CaballeroBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Suya WangBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Yulan AiBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Robyn J HylindBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Fujian LuBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Danielle A Heims-WaldronBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Kristina D ChambersBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Donghui ZhangBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Dominic J AbramsBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
William T PuBasic and Translational Cardiovascular Research and Inherited Cardiac Arrhythmias Programs, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (V.J.B., A.C., S.W., Y.A., R.J.H., F.L., D.A.H.-W., K.D.C., D.Z., D.J.A., W.T.P.).
Boston Children's Hospital · USDSM (Netherlands) · NL

Funding

RESEARCH METHODS IN PEDIATRICS HEART DISEASET32HL007572 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Sarah D DE FERRANTI, Jane W. Newburger · 1985 to 2026
$13.0M
Multi-scale modeling of inherited pediatric cardiomyopathiesUG3HL141798 · NHLBI · HARVARD UNIVERSITY · PI PARKER, KEVIN KIT, PU, WILLIAM TSWENCHING · 2017 to 2018
$2.6M
Novel molecular therapies for CPVTK08HL140197 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BEZZERIDES, VASSILIOS JAMES · 2018 to 2022
$851k
NHLBI NIH HHS K08 HL140197NHLBI NIH HHS T32 HL007572NHLBI NIH HHS UG3 HL141798
6 · The paper itself

Abstract

backgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited cardiac arrhythmia characterized by adrenergically triggered arrhythmias, is inadequately treated by current standard of care. Ca

methodsWe developed AAV9-GFP-AIP, an adeno-associated viral vector in which a potent CaMKII inhibitory peptide, autocamtide-2-related inhibitory peptide [AIP], is fused to green fluorescent protein (GFP) and expressed from a cardiomyocyte selective promoter. The vector was delivered systemically. Arrhythmia burden was evaluated with invasive electrophysiology testing in adult mice. AIP was also tested on induced pluripotent stem cells derived from patients with CPVT with different disease-causing mutations to determine the effectiveness of our proposed therapy on human induced pluripotent stem cell-derived cardiomyocytes and different pathogenic genotypes.

resultsAAV9-GFP-AIP was robustly expressed in the heart without significant expression in extracardiac tissues, including the brain. Administration of AAV9-GFP-AIP to neonatal mice with a known CPVT mutation (RYR2

conclusionsThis proof-of-concept study showed that AAV-mediated delivery of a CaMKII peptide inhibitor to the heart was effective in suppressing arrhythmias in a murine model of CPVT. CaMKII inhibition also reversed the arrhythmia phenotype in human CPVT induced pluripotent stem cell-derived cardiomyocyte models with different pathogenic mutations.

Indexed as

AdenoviridaeAnimalsAnimals, NewbornCalcium-Calmodulin-Dependent Protein Kinase Type 2Cells, CulturedGenetic TherapyMiceMice, TransgenicPolymorphic Catecholaminergic Ventricular TachycardiaTachycardia, VentricularCalcium-Calmodulin-Dependent Protein Kinase Type 2arrhythmias, cardiaccalcium-calmodulin-dependent protein kinase type 2death, suddengene therapypolymorphic catecholergic ventricular tachycardia

Identifiers

PMID31155924
PMCPMC7274838
OpenAlexW2948388341

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.