© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
New approaches to antiarrhythmic therapy: emerging therapeutic applications of the cell biology of cardiac arrhythmias1
* Corresponding author. Michael R. Rosen, Center for Molecular Therapeutics, College of Physicians & Surgeons of Columbia University, Department of Pharmacology, 630 West 168 Street, PH7W-321, New York, NY 10032, USA. Tel.: +1-212-305-8754; fax: +1-212-305-8351
Cardiac arrhythmias complicate many diseases affecting the heart and the circulation, and incorporate a multiplicity of underlying mechanisms. The evolution of scientific knowledge has made the complex changes produced by cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design in mechanism-specific and disease-specific fashion facilitates targeting of therapy via the methods of molecular, structural and translational biology. Additional approaches, employing similar drug design strategies but based on gene therapy and transcriptional and translational modification are on the horizon. Hence, there is reason to be optimistic regarding the design, testing and clinical availability of novel antiarrhythmic therapies.
Condensed Abstract: The evolution of scientific knowledge has made the effects of cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design facilitates targeting of therapy via the methods of molecular, structural and translational biology. Additional approaches, employing similar drug design strategies but based on gene therapy and transcriptional and translational modification are on the horizon. Hence, there is reason to be optimistic regarding the design, testing and clinical availability of novel antiarrhythmic therapies.
KEYWORDS Antiarrhythmic agents; Gene therapy; Genes
1 This manuscript will be published in Circulation and the European Heart Journal simultaneously.
* This paper summarizes the outcome of the Fourth Sicilian Gambit Meeting held in Chatham, Cape Cod, Massachusetts, 15–19 October 2000. The meeting was sponsored by the Basic Cardiovascular Sciences Council of the American Heart Association. Funding was arranged by Ernst Schneider and generously provided by an Educational Grant from Knoll AG. The meeting was organized by Edward Carmeliet, MD, PhD, University of Leuven, Belgium; Harry A. Fozzard, MD, University of Chicago, IL; Masayasu Hiraoka, MD, Tokyo Medical & Dental University, Japan; Michiel J. Janse, MD, Cardiovascular Research, Amsterdam, The Netherlands; Satoshi Ogawa, MD, Keio University, Tokyo, Japan; Dan M. Roden, MD, Vanderbilt University School of Medicine, Nashville, TN; Michael R. Rosen, MD, Columbia University, NY; Yoram Rudy, PhD, Case Western Reserve University, Cleveland, OH; and Peter J. Schwartz, MD, Policlinico S. Matteo IRCCS, Pavia, Italy. It was chaired by Dr. Rosen and co-chaired by A. John Camm, MD, St. George's Hospital Medical School, London, UK and Drs. Fozzard, Janse, Roden, and Rudy. Participating in the meeting and sharing in authorship of the paper are the above individuals as well as Charles Antzelevitch, PhD, Masonic Medical Research Laboratory, Utica, NY; Penelope A. Boyden, PhD, Columbia University, New York; William A. Catterall, PhD, University of Washington, Seattle, WA; Glenn I. Fishman, Mt. Sinai School of Medicine, New York; Alfred L. George, MD, Vanderbilt University Medical Center, Nashville, TN; Seigo Izumo, MD, Beth Israel Deaconess Medical Center, Boston, MA; José Jalife, MD, SUNY Syracuse, Syracuse, NY; Craig T. January, MD, PhD, University of Wisconsin, Madison, WI; André G. Kléber, MD, Universitaet Bern, Bern, Switzerland; Eduardo Marban, MD, PhD, The Johns Hopkins University, Baltimore, MD; Andrew R. Marks, MD, Columbia University, New York; Peter M. Spooner, PhD, NIH/NHLBI, Bethesda, MD; Albert L. Waldo, MD, Case Western Reserve University, Cleveland, OH; James M. Weiss, MD, UCLA Cardiovascular Research Laboratory, Los Angeles, CA; and Douglas P. Zipes, MD, Krannert Institute of Cardiology, Indianapolis, IN.