This Slimy Little Sucker Could Save Your Life

The leech, used for centuries to treat a variety of human ills and then abandoned with the rise of modern medicine, may be on the verge of new respectability thanks to recent breakthroughs in genetic engineering.

The slimy little bloodsuckers experienced a brief resurgence of medical interest several years ago, but they have been mostly relegated to the scummy ponds and swamps from which they came.

Now chemicals derived from leech saliva could finally provide their redemption. The substances, called hirudins, can be thought of as the chemical essence of leech. Their purpose is to stop blood from clotting while the 3-inch-long animals sip their suppers.

The chemicals have proved potent in preventing life-threatening blood clots in patients following hip replacement surgery, during heart attacks and in angioplasty, a procedure used to pry open the small arteries that nourish the heart.

A recently released international study showed that a leech-derived chemical could significantly reduce deaths and heart attacks in patients hospitalized with coronary artery disease.

The same hirudin, one brewed in baker’s yeast modified by genetic engineering, won federal approval for patients who develop life-threatening complications following the use of one of the most popular anti-clotting agents. A Boston area company is about to test a synthetic version of the drug, called Hirulog, on 17,000 heart attack patients around the world.

There is general agreement that the hirudins are extraordinary drugs, superior in several ways to some of the most commonly prescribed alternatives. But the companies that invested in them have suffered several costly disappointments on the way to market. Several have given up the chase and sold off their rights.

The issue is not whether the leech chemicals work--they clearly do--but whether they offer enough of an advantage over other, cheaper medications to justify the added expense.

“If we lived in a magical world and we didn’t have to consider cost, we’d immediately start prescribing Hirulog or hirudin,” said Dr. Elliott Antman, director of the coronary care unit at Harvard’s Brigham and Women’s Hospital. Compared with heparin, one of the most widely used clot-preventing drugs, hirudin is more reliable and requires fewer blood tests, Antman said. “But we don’t live in that magical world, and, as you know, budgetary issues now play a more frequent role in our discussions of medicines.”

But as science continues to test new approaches to cleaning out clogged arteries and veins, several companies are now betting on the leech--hoping that they have found ways to use hirudins in combination with other drugs to save health-care dollars as well as patients’ lives.

The number of individuals who could be affected are huge. More than 1 million Americans suffer from heart attacks each year and more than 430,000 undergo angioplasty, the American Heart Assn. estimates. For most of these patients, the use of drugs to prevent blood clot formation is now routine--with sales for some of the newer products exceeding $200 million a year.

Scientists searching for improved treatments for heart disease have learned important lessons from the European medicinal leech, Hirudo medicinalis, one of more than 600 species that swim the fresh waters of the world, feeding on the blood of other animals.

Historians trace its use back 2,500 years in India, China, Greece and Rome. But the leech reached its medicinal peak in the 19th century, when it “was considered a cure for nearly everything, including headache, fever, insomnia, ulcers and obesity,” writes Roy T. Sawyer, who has devoted much of his career to reviving the commercial use of the leech.

The rise of modern medicine questioned all forms of bloodletting, and by the 20th century, leeches had fallen out of therapeutic favor.

But thanks to Sawyer and others, leeches gradually won back a small role in medical treatment. For more than 20 years, some reconstructive surgeons have been using them to break up clots and remove congested blood in reattached body parts--especially fingers, ears and scalps.

And at least two companies--Leeches USA and Sawyer’s own Biopharm Leeches--supply the animals to hospitals throughout the country. Combined, the companies report selling 40,000 leeches a year at about $7 per animal.

It might take as many as 50 leeches applied over several weeks to save a reattached finger, hundreds of leeches to help restore a large flap of skin.

Although the animals bore in with their three-jawed mouths--each jaw lined with 100 tiny teeth--the procedure is remarkably pain-free. That’s probably because the animals first inject an anesthetic, said Leeches USA Vice President Rudy Rosenberg Sr.

It’s the chemicals in their saliva that have attracted the most intense medical interest.

The leech produces minute quantities of these substances, enough to stop clotting for a day or two in a reattached finger. But it would take thousands of them to produce enough hirudin to prevent clots in the veins and arteries of a desperately ill heart patient.

That problem was overcome a decade ago when scientists discovered how to produce the active compound in yeast or bacteria through genetic engineering.

Not long after, a scientist at Biogen Inc. in Cambridge, Mass., created Hirulog--a synthetic version of hirudin. The drugs were soon being tested in patients following heart attacks and during angioplasty--situations where the drug heparin has been used to block clot formation.

Heparin is an inexpensive standby that has been used to treat patients for a variety of conditions for 50 years. But it is not a perfect drug. Doctors must do repeated tests to make sure that the drug is preventing clots, but without excessive bleeding or strokes.

When Biogen and other companies began testing hirudins, the initial results were good--but not good enough. In 1994, Biogen said it would not seek Food and Drug Administration approval for Hirulog in angioplasty, and the company wrote off the drug as a $25-million loss.

Two years later, Ciba-Geigy, which has since merged into pharmaceutical giant Novartis, announced that its genetically engineered version of hirudin--called Revasc--had proved a disappointment in heart patients.

But last year, Medicines Co., a privately held drug development firm in Cambridge, Mass., paid Biogen $30 million-plus undisclosed additional fees for worldwide rights to the synthetic hirudin.

The company and its backers believe that Hirulog offers several advantages over heparin in both angioplasty and heart attack patients. The firm will be comparing the drug to heparin in 5,000 angioplasty patients and testing it in a trial of 17,000 heart attack patients.

Late last year, European researchers reported that Novartis’ Revasc had proved superior to a new version of heparin in blocking dangerous clots that frequently complicate hip replacement surgery. And last month Novartis licensed the drug, which has already been approved for use in Europe, to another pharmaceutical giant, Rhone-Poulenc Rorer. Although Rhone-Poulenc has not projected potential sales, the market is huge, with an estimated 1.2 million hip and knee replacements annually around the world.

Hoechst Marion Roussel this year won FDA approval for use of its genetically engineered hirudin, Refludan.

Several experts in cardiovascular disease are skeptical about the eventual role of the hirudins.

“The results in several large, well-designed studies have been largely disappointing,” said Dr. Gregg Fonarow, director of the UCLA Cardiomyopathy Center.

But others see the chemicals taking their place on the shelf along with other new approaches in the treatment of heart disease.

“There’s room in medical therapy for these drugs,” said Dr. A. Michael Lincoff, an associate professor of medicine at the Cleveland Clinic, and one of the principal investigators in the study of Hirulog in angioplasty. The evidence to date indicates that Hirulog is unlikely to be a “home run,” Lincoff said, but few drugs are.

“Medical science advances step by step in incremental progressions.”

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Times staff writer Paul Jacobs can be reached via e-mail at paul.jacobs@latimes.com.