Inducing ischemia and oxygen deprivation in this way caused a five-fold increase in the gene's activity in the heart, the researchers reported. That activity, in turn, resulted in a dramatic reduction in damage to the heart, Dzau said, with a significant 65 percent decrease in tissue death in animals treated with the gene construct compared to control animals. Skeletal muscle and liver exhibited a similar decline in injury following the gene therapy treatment.
In addition, one month later the untreated animals exhibited severe thinning of the heart wall and reduced heart function compared to those that received the gene therapy. After four months, the untreated rats still showed marked thinning of the heart wall, while those treated with the gene construct showed virtually no evidence of damage, Dzau said.
The team will next verify its results in another animal. If the findings hold, Dzau predicts the therapy might be ready to enter a phase I clinical trial in human patients in as little as a year. The adeno-associated vector used to insert the gene construct is already known to be safe for humans through its use in the treatment of hemophilia, noted Dzau.
Collaborators on the research include Alok Pachori, Luis Melo, Melanie Hart, Nicholas Noiseux, Lunan Zhang, Fulvio Morello, Scott Solomon, Gregory Stahl and Richard Pratt, all of Brigham and Women's Hospital.