Researchers trying to grow arterial bypasses

Tuesday, August 31, 2004

WASHINGTON -- Peter Cummins lay still as doctors administered 20 injections into the 81-year-old's calves and thighs, hoping the genetic experiment will spur new blood vessels to grow around his clogged leg arteries.

The experiment at the National Institutes of Health marks a resurgence in attempts to get the body to grow its own bypasses, at first in the legs and, if that works, perhaps later in the heart.

It's called therapeutic angiogenesis, a field that foundered a few years ago when early attempts proved disappointing. Now, a few companies are trying new approaches.

They're in the first stages of human testing with no way yet to predict success. Specialists are intrigued, however, because the experiments are based on a much-needed better understanding of complex artery-controlling genes.

It's an evolution that Dr. Brian Annex, Duke University's angiogenesis research director, characterizes as going from hype to hope.

"There definitely is a renewed interest," he said. This time around, "we've moved from the idea that this is an incredibly powerful magic bullet that you just have to have somewhere nearby and patients instantly get better. It was unrealistic to expect that."

The body sometimes reroutes blood flow around blocked arteries, particularly during peripheral artery disease, or PAD, which afflicts at least 12 million Americans like Cummins, of Falls Church, Va.

Their leg arteries stiffen and narrow, slowly choking off blood flow to muscles until patients find walking difficult. Cummins, for example, can go only about two blocks before getting an aching pain called claudication. In more severe cases, PAD can lead to amputation. And having it quadruples the risk of a heart attack or stroke, because if leg arteries are clogged, other blood vessels probably are, too.

In the late 1990s, scientists tried injecting PAD patients with proteins called growth factors -- the most famous was known as VEGF -- involved in growth of new blood vessels.

That proved too simplistic: when new arteries grew, they tended to be weak and leaky. It turns out different types of growth factors -- four forms of VEGF alone -- are needed in different amounts to react to different blockages, Annex explains.

"These are all delicate symphonies," said Dr. Robert Lederman of the NIH's National Heart, Lung and Blood Institute in describing the body's artery-growing machinery.

So instead of trying to manipulate just one part of the machinery, there's a new focus on jump-starting the overarching genes that control the process and letting the body finish the job naturally.

There's no way to know if any of the research will pan out. If nothing else, the new research is focusing important attention on PAD, said NIH's Lederman. Too many people consider trouble with walking merely a consequence of aging, not disease.

"At my age, if it doesn't work, it doesn't work," said Cummins. "But if this works out, I'm sure hoping it'll motivate other people to participate in studies such as this, with the outlook that mankind is going to benefit."

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