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Gene therapy alternative to calcium channel blockers

In animal studies, scientists at Johns Hopkins have developed what is believed to be the first successful gene therapy that mimics the action of calcium channel blockers, agents widely used in the treatment of heart diseases, including angina, arrhythmias, hypertension and enlarged heart.

Their findings published in the latest edition of Circulation Research, online July 8 may lead to a gene therapy alternative to calcium channel blockers and their sometimes severe side effects, but also further interest in the development of gene therapies unique as in this case to one particular organ.

Using guinea pigs, the Hopkins team increased production of a key protein involved in heart conductivity, called G-protein Gem, by injecting a virus carrying the gene that codes for the protein into the animals' heart muscles.

Increased levels of Gem decreased calcium current densities the chemical action of calcium channel blockers by 30 percent to 90 percent, when compared to a control group.

Indeed, when heart muscle was electrically stimulated to reproduce the effects of an irregular heartbeat, Gem infusion helped steady the heartbeat, returning it to a normal rhythm, just like calcium channel blockers do. No adverse side effects were observed.

"Calcium channel blockers are a valuable tool in combating arrhythmias and other forms of heart disease, but they can cause low blood pressure, heart block and constipation," said study lead author and cardiovascular physiologist Eduardo Marbn, M.D., Ph.D., professor and chief of cardiology at The Johns Hopkins University School of Medicine. Marbn is also director of the Hopkins Institute of Molecular Cardiology and editor in chief of Circulation Research. "Our basic research is trying to find new ways of harnessing the benefits of calcium channel blockers, while avoiding the negative side effects of existing pill therapies, especially on other organs of the body. Our initial results with gene therapy
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
8-Jul-2004


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