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Heartless worms hold clues to cardiac arrhythmias, sudden death

Could help lead to development of drugs that don't cause calcium channel block

The worm C. elegans seems an unlikely candidate for studies related to cardiac arrhythmias. After all, the microscopic organism doesn't even have a heart.

That fact did not deter Christina I. Petersen, Ph.D., research assistant professor of Anesthesiology at Vanderbilt University Medical Center. Petersen and colleagues, including Jeffrey R. Balser, M.D., Ph.D., associate vice chancellor for Research at Vanderbilt, have now developed a C. elegans-based screening tool to identify novel protein regulators of a potassium channel involved in the rhythmic heartbeat.

They report the success of their approach in the Aug. 10 issue of the Proceedings of the National Academy of Sciences. The tool could lead to ways to prevent arrhythmias and sudden death associated with block of a potassium channel called HERG (Human ether-a-go-go related gene).

Many therapeutic drugs -- antihistamines, antidepressants, antibiotics -- block HERG, Petersen said. This undesired blockade can cause acquired long QT syndrome, a disorder that puts patients at risk for life-threatening arrhythmias. It is not clear why some individuals receiving a HERG-blocking drug develop the syndrome, Petersen said.

"It's a serious problem," she said. "The FDA now requires that every drug be assayed for HERG block before it is approved." Even medicines that might be beneficial for the vast majority of patients do not make it to the market or have been pulled from the market -- if they block HERG, Petersen said.

"The pharmaceutical industry is very interested in finding ways to screen for susceptibility to acquired long QT syndrome and in discovering how to prevent it."

Other investigators have demonstrated that variations in HERG itself do not account for the majority of interindividual differences. Petersen and colleagues suspected that other proteins -- modula
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19-Aug-2004


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