Antiarrhythmic gene therapy - will biologics replace catheters, drugs and devices?

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• 作者：Patrick Lugenbiel^a ; Patrick A. Schweizer^a ; ^b ; ^c ; Hugo A. Katus^a ; ^b ; Dierk Thomas^a ; ^b ; ^{Dierk.Thomas@med.uni-heidelberg.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AERP ; atrial effective refractory period ; AF ; atrial fibrillation ; AP ; action potential ; APD ; action potential duration ; AV ; atrioventricular ; CHF ; chronic heart failure ; CPVT ; catecholaminergic polymorphic ventricular tachycardia ; ERG ; ether-a-go-go-related gene ; HCN ; hyperpolarization-activated ; cyclic nucleotide-gated channel ; LAD ; left anterior descending artery ; LBB ; left bundle branch ; MSC ; mesenchymal stem cells ; SCD ; sudden cardiac death ; SERCA ; sarcoplasmic reticulum Ca2+ ATPase ; SND ; s
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：264-273
• 全文大小：379 K

文摘

The clinical management of heart rhythm disorders still constitutes a major challenge. The development of alternatives to current approaches is of significant interest in order to establish more effective therapies that increase quality of life and reduce symptoms and hospitalizations. Over the past two decades the mechanistic understanding of pathophysiological pathways underlying cardiac arrhythmias has advanced profoundly, opening up novel avenues for mechanism-based therapeutic approaches. In particular, gene therapy offers greater selectivity than small molecule-based or interventional treatment. The gene of interest is packaged into viral or non-viral carriers and delivered to the target area via direct injection or using catheter-based techniques, providing the advantage of site-restricted action in contrast to systemic application of drugs. This work summarizes the current knowledge on mechanistic background, application strategies, and preclinical outcome of antiarrhythmic gene therapy for atrial fibrillation, ventricular tachycardia, and modulation of sinus node function.