Gene Transfer Makes Hearts Beat Stronger - Technology Information

Applied Genetics News, April, 1999

In an article published in the current issue of the journal Circulation by Collateral Therapeutics (9360 Towne Centre Dr., San Diego, CA 92121; Tel: 619/824-6500, Fax: 619/824-6563), founder H. Kirk Hammond supports the viability of gene therapy as a treatment for congestive heart failure (CHF).

The study, carried out by Hammond and colleagues at the Veterans Affairs Medical Center and University of California, San Diego, found that inserting a gene called AC-6 boosts production of adenyl-cyclase and makes the heart beat stronger. The strength of the heartbeat is controlled by several messengers working in sequence.. When stress or exercise calls for more blood, epinephrine and norepinephrine are released. These hormones bind with specific receptors on the surface of cardiac cells, which transmit the message to the enzyme adenylate-cyclase. This enzyme produces cAMP, which is ultimately responsible for commanding the heart to pump. In CHF patients, however, there is no increase in cAMP despite stimulation by norepinephrine. The Circulation paper compares transgenic mice to non-transgene mice from the same litter to determine whether increased quantities of AC-6 would boost cAMP in response to catecholamine stimulation. Mice containing the AC-6 gene produced three to four times more cAMP than the control group and experienced a two-fold increase in contractile function. The increased heart function persisted in very old mice and was not associated with negative effects. "We are excited about these data because they provide additional evidence that it may be possible to increase heart function safely and effectively through gene transfer," says Hammond, who is an associate professor of medicine at UC San Diego, and vice president of research at Collateral.