Gene treatment can boost heart function in rabbits, Duke resea...( d by ßARK an enzyme inside the c...)

In 1994, Lefkowitz, Koch and their colleagues showed that mice genetically altered to produce excess beta adrenergic receptors (ßARs) have supercharged hearts that beat faster and stronger than a normal mouse's heart. In 1997, the researchers inserted a gene that encodes the ßAR into an adenovirus.

"Our studies have shown that a malfunctioning beta adrenergic receptor system greatly contributes to heart failure," Koch said. "By contrast, boosting levels of beta adrenergic receptors or inhibiting ßARK can reverse heart failure in genetic mouse models. Now, we are beginning to see the same result when we deliver these genes to rabbits."

In their earlier test tube experiments Koch and his colleagues allowed the virus to infect isolated failing rabbit heart cells. They found that the inserted ßAR genes produced up to 15 times the normal amount of the ßAR protein found in rabbit cells, which restored normal heart signaling.

In the current experiments, the animals' heart cells produced the equivalent of 10 times the normal number of ßARs. As a result, they shows a 20 percent increase in the force of their heart contractions.

In addition, the researchers tested the effects of a range of concentrations of ßARs and found that as they increased ßAR, they increased the force of contraction to a maximum of 20 percent.

The researchers tested whether the ßARs would respond to the drug isoproteronol, which stimulates ßARs. When researchers injected the drug into both normal rabbits and rabbits with the additional ßARs, they found the rabbit hearts with the additional ßARs responded to the drug even more
'"/>

Contact: Karyn Hede
Hede0001@mc.duke.edu
919-684-4148
Duke University Medical Center
30-Jun-1999