Biological Therapies for Cardiac Arrhythmias

Michael R Rosen
US Cardiology, 2009;6(1):85-88
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Abstract

Over the past 50 years cell and then gene therapy have been attempted for a variety of diseases, with varying success and toxicity. During the past decade both approaches have been applied to arrhythmia therapy. This brief review summarizes the successes achieved and challenges confronting this burgeoning field in its initial years of growth. In the treatment of bradyarrhythmias, biological pacemakers are well-advanced into proof-of-concept and there efforts to repair/replace the diseased atrioventricular node have begun. In tachyarrhythmia therapy, a number of ion channel constructs targeted at specific ion channels are under assessment. All therapies at present have both viral gene therapy and cell therapy arms. It is estimated that this dichotomy will continue until one or another approach is found to be definitively advantageous.
Keywords
Ventricular tachycardia, ventricular fibrillation, atrial fibrillation, heart block, embryonic stem cells, mesenchymal stem cells, viral vectors
Disclosure The author has no conflicts of interest to declare.
Received: December 23, 2008 Accepted January 30, 2009
Correspondence: Michael R Rosen, MD, Center for Molecular Therapeutics, Columbia University, PH 7W-321, 630 West 168 Street, New York, NY, 10032. E: mrr1@columbia.edu

Cardiac arrhythmia diagnosis is as old as the Bible and ancient Chinese literature.1 Treatment has progressed from the natural products used by the ancients, to formalized attempts at pharmacological therapy over the last 300 years (with digitalis and cinchona bark being the lead compounds), to the modern use of devices and ablation. However, with the exception of electronic pacing for atrioventricular (AV) block and related arrhythmias, all therapies used have had significant drawbacks. These range from the pro-arrhythmic consequences of many antiarrhythmic drugs to the inappropriate shocks delivered by cardioverter–defibrillators, and have provided the impetus for exploring the possibilities afforded by emerging cell and gene therapies.

Biological Therapies

Autologous biological therapies achieved widespread use in the 20th century in the form of bone grafting, skin grafting, and tendon transplants. The use of allogeneic biological sources has become commonplace in replacing kidneys, hearts, lungs, and livers, although in all of these instances a key component to success has been the advances in immunosuppression that prevent rejection. Two breakthroughs have been particularly responsible for advances in modern cell therapy: bone marrow transplant (either autologous or heterologous2) and the isolation and study of mammalian and, later, human3 embryonic stem cells. We can now look with near certainty to being able to coax cells into developing along specific lineages to repair and/or replace diseased organs. Currently, experimentation proceeds with the embryonic stem cell, whose pluripotency makes it a progenitor of all cell and organ types in the body, with induced pluripotent stem cells (the product of adult fibroblasts engineered to return to an embryonic status from which they can then be grown along specific lineages), and with adult human mesenchymal stem cells (hMSCs), which are multipotent and can differentiate into mature lineages or serve as vehicles for carrying genes and small molecules to target organs.

Limits to progress are seen only in the fits and starts of the scientific discovery process but, for human embryonic stem cell research, also in sociopolitical and religious reservations. How long will it take before we see consistently successful clinical outcomes? A different high-impact discovery may provide some perspective.

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