In the current experiments, the effect of the introduced genes lasted for about three weeks. Koch said that he believes the immune system eventually clears the adenovirus from the body, eliminating the therapeutic effect. Koch emphasized that more effective methods of carrying the genes into cells need to be developed before gene therapy for heart failure in people becomes a practical option. The researchers say that with the development of improved viruses and other vehicles to introduce genes into the heart, the technique might be used on congestive heart failure patients within the next decade.
The latest achievement built on earlier basic studies in the lab of Dr. Robert Lefkowitz, a Howard Hughes Medical Institute investigator at Duke. Using mouse models and sophisticated genetic techniques, Lefkowitz and his colleagues identified the molecules responsible for fostering efficient pumping action in the heart and showed which ones can make the heart function more efficiently. The Duke scientists showed that two key proteins in heart cells -- called beta-adrenergic receptors (ßARs) and beta adrenergic receptor kinase (ßARK) -- work together to regulate heart function. Receptors such as ßAR are molecular switches that turn on cell processes when triggered by external substances such as hormones.
In reacting to a failing heart, the body releases large amounts of the hormone
norepinephrine directly into the heart. This norepinephrine binds to ßARs on the
surface of heart cells, triggering the heart to work up to five times harder
than normal. While this overstimulation initially allows the heart to increase
the power of its contractions, in heart failure the stimulation quickly becomes
self-defeating, because the receptors become desensitized, meaning they no
longer respond to hormone stimulation.
This desensitization is cause
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Contact: Karyn Hede
Hede0001@mc.duke.edu
919-684-4148
Duke University Medical Center
30-Jun-1999