Tumor Drug for the Heart?

A widely heralded but still experimental cancer-fighting compound may be used someday to prevent two other major killers of Americans: heart disease and stroke. That was the implication of a remarkable report published last week in the journal Circulation by a team of researchers from Dr. Judah Folkman's laboratory at the Children's Hospital in Boston.

The versatile compound is endostatin, a human protein that inhibits angiogenesis, the growth of new blood vessels in the body. In tests reported in 1997 by Folkman, a prominent cancer researcher who pioneered the study of angiogenesis, the drug had reduced and even eradicated tumors in laboratory mice. How? By stunting the growth of capillaries necessary for nourishing the burgeoning mouse tumors.

When news of Folkman's achievement became widely known last year, it led to wildly exaggerated predictions of imminent cancer cures. When other scientists were initially unable to duplicate those results, questions arose about the validity of Folkman's research. Then in February scientists at the National Cancer Institute, with guidance from Folkman, finally matched his results. Reassured, the N.C.I. gave the go-ahead for clinical trials of endostatin later this year on patients with advanced tumors.

How can a drug that is apparently effective against tumors also reduce the risk of heart attack and stroke? The answer lies in the composition of plaque, the fatty deposit that builds up in arteries and can eventually clog them. Plaque consists of a mix of cholesterol, white blood cells and smooth muscle cells, and as it accumulates, a network of capillaries sprouts from the artery walls to nourish the cells. Could endostatin halt the growth of capillaries and starve the plaque?

A Folkman lab team led by Dr. Karen Moulton decided to find out. The scientists put baby lab mice on a 16-week "Western diet" that was high in fat and cholesterol, then measured the plaque buildup on the walls of each aorta, the large artery that carries blood from the heart to the rest of the body. Meanwhile, they injected one group of mice with endostatin, another with a different blood-vessel inhibitor called TNP-470 and a control group with an inert saline solution. Twenty weeks later the researchers again measured plaque in the mouse aortas. The results were startling: the endostatin group averaged 85% less plaque buildup and the TNP-470 group 70% less than those in the control group.

All too aware of the premature hopes raised last year after Folkman's tumor report, the researchers have been careful not to oversell the new results. "If this finding is supported in future studies," says Moulton, "[it could open the way for] treatments that could delay the progression of heart disease and possibly reduce the incidence of heart attacks and strokes." But any such treatments, she stresses, are probably five to 10 years away.

--By Leon Jaroff