The report is the latest in a growing field with this guiding idea: If you can't reopen a blocked vessel or bypass it, then grow new vessels to restore blood flow, either by gene therapy or by using vessel-promoting molecules.
The molecule used by the researchers is granulocyte-macrophage colony-stimulating factor (GM-CSF), one of several proteins that act to promote production of blood cells and platelets. GM-CSF supports the growth of white blood cells called macrophages, which is why it is given to cancer patients with leukemia and those who have bone marrow transplants.The use of GM-CSF in patients with severe coronary artery disease was based on studies showing that macrophages induce the growth of new blood vessels, a group led by Dr. Christian Seiler, a cardiology professor in Bern, reports in the Oct. 23 issue of Circulation: Journal of the American Heart Association.
The study enlisted 21 patients whose coronary artery disease was too severe to be treated either by angioplasty, which reopens a blocked artery, or bypass surgery, which sews in a vessel around the blockage. One of five patients with coronary artery disease is ineligible for angioplasty, and one in three is ineligible for bypass.
The Swiss researchers gave 10 patients injections of GM-CSF every other day for two weeks; the other 11 got injections of a placebo, an inactive substance. At the end of the two weeks, the GM-CSF patients showed measurable improvement in blood flow, while the blood flow had worsened in those who got the placebo.
"Our clinical study provides proof of GM-CSF's potential to enhance the growth of coronary blood vessels," says a statement by Seiler.
The patients will be followed for a year to see if the results last.
GM-CSF is not the first such protein to be used for angiogenesis, the growth of new blood vessels, says Dr. Julie M. Miller, associate professor of medicine at Johns Hopkins Hospital in Baltimore. She is a member of the Peripheral Atherosclerosis Research Consortium, which has used fibroblast growth factor to improve blood flow for patients with artery blockages in the legs.
"The initial results look promising," Miller says. "There was a favorable trend in the patients' ability to walk."
Other angiogenesis researchers have used injections of vascular endothelial growth factor or have inserted the gene for that growth factor into heart cells to improve blood flow in the heart.
Many of those studies have been done at the Angiogenesis Research Center of Harvard Medical School. Although researchers there have used several growth factors in their studies, the Swiss are the first to use GM-CSF, says Dr. Roger Laham, director of the Harvard center.
And, he adds, although the number of patients in the Swiss study is small, the implications are potentially important.
"This is a hypothesis-generating study," he says.
What To Do
Angiogenesis therapy for coronary artery disease is in the research stage, and has to go through a number of trials using different agents before it will arrive in your cardiac treatment center.
For a glimpse of what is happening at one major research center, go to the Harvard Medical School Angiogenesis Research Center. For a look at the toll heart disease takes in this country, visit the American Heart Association.