Biological Therapies for the Treatment of Cardiac Arrhythmias (original) (raw)

The large number of publications reporting advances in vector design, gene transfer protocols and stem cells manipulation prompted the expectation that these methods may become available to the clinicians. However, since the technological transfer from the bench to clinical practice demands that aspects such efficiency, long term effect of the therapy and its safety are elucidated, the development of the field has been slower than anticipated. The use of biological therapies in the management of cardiac arrhythmias to overcome the limitations of pharmacological, ablative and device treatments has attracted a strong interest from the arrhytmologists. Although the availability of such treatments in clinical cardiology, is still far ahead, various research groups are conducting preliminary but very encouraging investigations supporting the view that rhythm manipulation by biological means is a feasible approach at least in animal models. In this review we will discuss the approaches that have been outlined in the experimental laboratories for the control of rhythm disturbances. Three key strategies for biological therapies of cardiac arrhythmias will be presented: 1) the use of viral vectors to modulate molecular targets that are critical for the control of excitability (gene delivery), 2) the use of modified stem cells to recreate specialized structures such as the sinus node or the atrio-ventricular node (cell graft), 3) the application of post transcriptional modulation to control the production of substances that may attenuate the arrhythmogenic potential of different diseases (expression modulation). We will analyse the pros and cons of these approaches and will conclude by discussing the unmet needs and the challenges in this field.