"Immediately following a heart attack, blood vessels near the site of injury become leaky, causing fluid accumulation in the healthy area of the heart surrounding the injured site," says Immunology Professor David A. Cheresh, Ph.D., who led the research with postdoctoral fellow Sara Weis, Ph.D at The Scripps Research Institute. This permeability response is devastating to normal heart tissue.
"Until now," continues Cheresh, "nobody has realized the extent to which this leak response damages heart tissue and causes long-term tissue injury. We discovered a way to block this process and thus save heart tissue from irreversible damage."
Using laboratory models that are designed to mimic the pathology of heart attacks in humans, Cheresh, Weis, and their colleagues found that a single dose of a compound designed to block this fluid leakage (which is called edema) can, even if given as late as six hours after the event, drastically reduce tissue injury and increase long-term survival following a heart attack.
A biopharmaceutical company, TargeGen Inc. in San Diego, is finalizing preclinical studies to translate these initial research findings into practical human therapies. Using extensive preclinical models that mirror human heart attacks, TargeGen scientists report that 40 to 60 percent reductions in infarct (tissue injury) size with a small molecule drug that inhibits vascular leak and edema. Based on the encouraging preclinical efficacy and safety studies, TargeGen plans to initiate a combined Phase I/II human clinical trial in the second half of 2004 for patients undergoing an acute heart attack.