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Helping hamster hearts with a therapeutic gene
  

 

A five-year project to test gene therapy for heart failure has scored a success in hamsters, and the researchers say clinical trials in humans could begin within two years.

By delivering a human gene to weakened hamster hearts, the researchers staved off heart failure in the animals for up to seven months. The hamsters had a heart condition similar to one in humans. For many patients with chronic heart failure, the only treatment is heart transplantation, and the waiting lists for this operation far outnumber the available organs.


Hamster hearts with cardiac interstitial fibrosis (left) and reduced fibrosis after gene delivery (right).

The most common form of heart failure occurs after a heart attack. With more and more individuals surviving heart attacks, the incidence of heart failure has likewise increased and created an urgent need for new therapies.

In the study, Kenneth R. Chien, of the University of California, San Diego, and colleagues inserted a modified human gene into the muscle cells of hamster hearts. The gene, called phospholamban (PLN), overrides an unhealthy 'braking' action on the cardiac pump, which can cause chronic heart failure.

"We were astonished and surprised by the amount of cells affected and for the duration of time," Chien says.

The mutated gene was expressed in 60 percent of the heart muscle cells and halted further muscle damage in the hamsters for 28 to 30 weeks, according to the study published in Nature Medicine.

The researchers used a modified virus, called recombinant adeno-associated virus vector, to deliver the PLN gene throughout the cardiac muscle. They used the virus because it could go undetected by the hamster's immune system and stabilize itself in the heart muscle cells.

The study has been extended to pigs, with plans to progress to human clinical trials in the next year and a half, according to the researchers. They are currently investigating a delivery system in pigs that uses a catheter to inject the therapeutic gene directly into the coronary artery.

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Hoshijima, M. et al. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med. Published online July 21, 2002.
 

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