Columbia University Medical Center

Strides Made Toward A Genetically Engineered Way Of Treating Arrhythmias

Columbia Work Highlighted in Latest Journal of Physiology

NEW YORK (April 15, 2009) – A team of scientists at Columbia and Stony Brook Universities is at the forefront of new developments in the engineering of biological pacemakers for the treatment of abnormally slow heart rates.

New research by members of the team provides further evidence that biological pacemakers may render conventional electro-mechanical pacemakers an outmoded way of treating prevalent and persistent heart conditions. About 3 million people worldwide carry implanted electro-mechanical pacemakers, and each year about 600,000 pacemakers are implanted. Through genetic engineering techniques, the team has turned a small fraction of heart muscle cells into specialized “pacing” cells that have a faster, regular, beating pattern, creating a “biological pacemaker.”

X-ray image of an implanted, electro-mechanical pacemaker.

Consider this: mechanical pacemakers, implanted surgically, have several limitations including electrode fracture, damage to insulation, infection, re-operations for battery exchange, and vein thrombosis. Fully aware of the drawbacks associated with artificial devices, the Columbia and Stony Brook researchers have been exploring the use of a specific gene family, the HCN (Hyperpolarization-activated Cation Channels) pacemaker family, as biological pacemakers. This gene family contributes to normal pacemaker function in the heart, and biological pacemakers aim to replicate and enhance this functionality when the normal process fails.

One challenge to this work has been developing a convenient model to evaluate different HCN gene modifications to optimize the biological pacemaker. The present work, published in the most recent edition of The Journal of Physiology and highlighted by two editorials in the same issue, addresses this problem. Researchers at Columbia University Medical Center and Weill Medical College of Cornell University in New York City collaborated in a study using genetically engineered heart cells in culture and computer simulation to evaluate both naturally occurring and engineered ion channels for use in development of a biological pacemaker.

Richard Robinson, Ph.D., associate dean for graduate affairs; professor of pharmacology in the Center for Molecular Therapeutics.
Different HCN channels were expressed in heart cells. Channel parameters and the effect on spontaneous rate were measured, and the channel parameters were entered into a computer simulation to explore their contribution to the rate effect. The biological pacemaker appears to respond to the body’s signals in the same manner as the heart’s native pacemaker, yet it requires no batteries or replacement of electrical stimulator leads and could last a lifetime.

According to lead researcher Richard B. Robinson, Ph.D., professor of pharmacology at Columbia University’s College of Physicians & Surgeons, the latest development “will facilitate the development of practical biological pacemakers by allowing more complete and rapid assessment of individual channel mutations through combined culture and simulation studies prior to full testing in animal models.”

In addition, the HCN-expressing heart culture system could serve as a screening assay for new pharmacological agents to regulate heart rate.

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