Blocked Arteries? Grow New Ones

Recent breakthroughs in gene therapy up the biotech ante

After years of failures in gene therapy, Dr. Jeffrey M. Isner and his colleagues at St. Elizabeth's Medical Center in Boston have scored an impressive advance. They are injecting growth genes near the clogged leg arteries of patients, triggering formation of new blood vessels to bypass the blockages. The report of the research on Nov. 9, at the American Heart Assn.'s annual scientific meeting, excited the medical Establishment--and upped the stakes in one of biotech's hottest races.

Isner aims to use growth genes to treat the clogged coronary arteries that are a major cause of heart attacks. But in that quest, he already has company. Genentech Inc. has used a related technique on 35 coronary patients. And Warner- Lambert Co. is backing work by GenVec Inc. to deliver a blood-vessel growth gene via a patented virus.

ONE OF THE FIRST. All the techniques have huge promise as an alternative to the 500,000 bypass operations and 400,000 angioplasties done each year in the U.S. Even if the new therapies are used only as a companion treatment to those procedures, the demand could be enormous. "This clearly is a several-billion-dollar market, were you to actually succeed," says Dr. Elliott Grossbard, senior vice-president for Scios Inc., a Mountain View (Calif.) biotech company working on growth-gene therapies.

It may be years before the research on these new treatments is concluded, but that's not slowing the race to develop a commercial product. The day after he presented his findings, based on work on nine patients, Isner announced he is teaming up with Human Genome Sciences (hgs), St. Elizabeth's Medical Center, and Cato Holding to form a company called Vascular Genetics Inc. hgs, which discovered one of the growth-factor genes, is loaning Vascular Genetics the money it needs and taking a 19.9% stake.

Isner's technique--one of the first gene-therapy successes in patients--is simple. He injects a growth-promoting gene into muscle near the clogged artery. The gene is one of several now known to make so-called vascular endothelial growth factors. These vegf genes are what the body uses to promote blood-vessel growth. The genes are picked up by the muscle cells, which then make a vegf protein. That protein spurs the growth of new arteries.

Genentech, meanwhile, is using vegf proteins made in the lab and injected into patients intravenously or directly into their coronary arteries. Is the treatment working? "Without getting into the specifics, we plan to continue going forward," says Ted W. Love, vice-president for product development.

Isner believes either approach can work. But he argues that his gene therapy is far less expensive. Making genetically engineered proteins requires at least a $20 million investment, he says, and the proteins are expensive to manufacture. "Theoretically, you could have two companies, and the one making dna could vastly undersell the other," he says. Love won't say what Genentech is spending on vegf research. But developing a drug could cost $300 million to $500 million, he says.

GenVec, meanwhile, has a deal that could be worth more than $100 million with Warner-Lambert. GenVec has licensed a vegf gene from Scios and has used a modified virus to deliver it to the hearts of more than 100 pigs. GenVec is now preparing to start human trials.

Isner is waiting for Food & Drug Administration approval to begin tests on coronary arteries, and he plans a larger study of limb arteries. Whatever the outcome, he has already helped harness the biotech revolution in pursuit of the nation's No.1 killer.

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