Gene therapy to restore electrophysiological function in heart failure

Lukas J. Motloch, Fadi G. Akar

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Heart failure (HF) is a major public health epidemic and a leading cause of morbidity and mortality in the industrialized world. Existing treatments for patients with HF are often associated with pro-Arrhythmic activity and risk of sudden cardiac death. Therefore, development of novel, effective and safe therapeutic options for HF patients is a critical area of unmet need.Areas covered: In this article, we review recent advances in the emerging field of cardiac gene therapy for the treatment of tachy- and bradyarrhythmias in HF. We provide an overview of gene-based approaches that modulate myocardial conduction, repolarization, calcium cycling and adrenergic signaling to restore heart rate and rhythm.Expert opinion: We highlight major advantages of gene therapy for arrhythmias, including the ability to selectively target specific cell populations and to limit the therapeutic effect to the region that requires modification. We illustrate how advances in our fundamental understanding of the molecular origins of arrhythmogenic disorders are allowing investigators to use targeted gene-based approaches to successfully correct abnormal excitability in the atria, ventricles and conduction system. Translation of various gene therapy approaches to humans may revolutionize our ability to combat lethal arrhythmias in HF patients.

Original languageEnglish (US)
Pages (from-to)803-817
Number of pages15
JournalExpert Opinion on Biological Therapy
Volume15
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Arrhythmias
  • Calcium
  • Conduction
  • Gene therapy
  • Heart failure
  • Repolarization

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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