'Biological Bypass' Saves Hearts Sans Surgery

THE GIST:

• A "biological bypass" could eliminate heart surgeries.
• Instead of unplugging clogged arteries, the biological bypass would create new ones.
• FDA approval for these drugs for use in humans is still about five to 10 years away.

Why bother cleaning clogged arteries when you can simply grow new ones?

Scientists from Yale University have developed a "biological bypass" around a life-threatening blocked artery. The research could reduce or even eliminate the need for invasive surgery while preventing heart attacks before they become an issue.

"Instead of doing a surgical bypass or stenting, you could induce the growth of new arteries with a biological bypass," said Michael Simons, a doctor at Yale University and co-author of a recent paper in the Journal of Clinical Investigation. "This would be a major step in how we treat cardiovascular disease."

Clogged arteries can kill a person through heart attacks, strokes and other medical emergencies. For years doctors have cleaned clogged blood vessels by inserting a balloon into an artery and expanding it. The balloon compresses fatty deposits that build up on the walls of arteries, and opens blood vessels. If the vessel is plugged beyond repair, doctors remove the offending artery and replace it with another blood vessel, usually one from the patients leg -- an invasive and costly procedure.

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The Yale doctors have proposed a different solution: Instead of repairing broken blood vessels, they want to grow new ones. The new arteries would bypass the clogged areas and restore blood flow without an incision.

A biological bypass is not a new idea. Other groups in the 1990s and early 2000s tried various growth factors -- drugs that directly encourage the creation of new arteries -- but this approach never really panned out.

The Yale scientists decided attack the problem another way. Instead of directly encouraging the growth of new arteries, they would discourage blood vessel inhibition.

The researchers found that two drugs that take this sort of "enemy of my enemy is my friend" approach. The drugs, known as PI3-kinase inhibitors, disable a specific enzyme that prevents the growth of new blood vessels. Turning off PI3 means another pathway, which triggers the growth of new blood vessels, can turn on.

The drug only encourages new arterial blood vessels to form. Capillaries, blood vessels so small a red blood cell has to squeeze through, aren't affected by the drug. That's good news for oncologists and patients with cancer, says Simons and William Chilian, a doctor and professor at Northeastern Ohio University.

By understanding which molecular pathways stop or start the production of new blood vessels, scientists can create new drugs to manipulate these pathways. "There is no question this research could impact cancer research," said Chilian.

Many cancers release chemicals that encourage the growth of new blood vessels. The new blood vessels supply tumors with the blood and oxygen they need to grow. Block new blood vessels, oncologists hypothesize, and you block the tumor.

It will takes years before cardiologists or oncologists can use the research to treat actual patients. The Yale experiments were done in fish and mice, and only for a three weeks at a time. The PI3-kinase inhibitor is already in Food and Drug Administration drugs trials, but for cancer, not heart disease. Approving the drug for heart disease will take an estimated five to 10 years to complete, if future experiments are successful, said Simon.

Nevertheless, "this research is a great first step," in understanding the signaling process that encourages blood vessel growth, said Chilian. "It allows us to understand why the trials using growth factors went wrong, and could eventually allow patients to grow their own bypass."