NEW YORK (Reuters Health) - A new animal study provides proof of concept that preemptive administration of gene therapy could prevent both short- and long-term tissue damage after heart attack or stroke.
An adeno-associated vector consisting of erythropoietin hypoxia response elements (HREs), which activate genes in response to hypoxic conditions, and the human heme-oxygenase-1 (hHO-1) gene was able to prevent ischemia/reperfusion injury in rats, Dr. Victor J. Dzau and colleagues from Harvard Medical School in Boston report.
The researchers injected the vector into the heart, liver and skeletal muscle of the animals, inducing ischemia/reperfusion injury 5 weeks later. In animals that were not injured, hHO-1 expression was not detected. But the injury in skeletal muscle, liver and heart tissue briefly induced hHO-1 expression.
Less injury occurred in the animals treated with the gene vector than in those given a control vector, and expression of proinflammatory cytokines was lower. In the hHO-1 treated animals, infarct size was 65% smaller than in the control mice (p < 0.01).
At 1 and 4months after the injury, the hHO-1 treated mice had near-normal heart function and anatomy, while the control animals showed pathological remodeling of heart tissue and impaired heart function.
The next step, Dzau told Reuters Health, will be to investigate the vector in pigs. He added it would be possible to start phase 1 trials within a year, although logistical concerns may extend the timeline.
Dr. Dzau anticipates that patients at high risk of myocardial infarction could be given the vector while angioplasty is performed.
Efforts to use drugs and gene therapy to prevent ischemia and reperfusion face a number of hurdles, Dr. Dzau notes, among them the difficulty of administration during the critical 4- to 6-hour post-MI window. The preemptive approach would sidestep this issue.
In animals expression of the gene has been seen 1 year after administration of the vector, he added, and it is safe to anticipate that the gene would last for several months in humans.
Source: Proc Natl Acad Sci USA Early Edition 2004. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Therapy: Disease Models, Animal: Genetic Engineering: Genetic Techniques: Investigative Techniques: Therapeutics: Gene Therapy: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
