Old drug has new potential

EPO: A popular medicine for anemics holds promise for a range of other conditions, including stroke, heart attack and spinal cord injury.

Medicine & Science

May 24, 2004|By David Kohn | David Kohn,SUN STAFF

In 1987, neurologist Hannelore Ehrenreich noticed something odd in anemic patents being treated with a drug called erythropoietin. After taking the drug for just a few days, they seemed mentally sharper and more alert.

After several years studying the drug's effect on brain cells, she had an inspiration: Maybe the anemia drug could also heal brain damage caused by strokes.

Among colleagues, her theory was not a hit. "People laughed at me. They said I was crazy," remembers Ehrenreich, a researcher at the University of Gottingen in Germany. But 12 years later, her notion looks increasingly prophetic.

Erythropoietin, known as EPO, is showing promise not only for stroke, but also for a wide range of ailments including heart attack, multiple sclerosis, spinal cord injury, and nerve and intestinal problems. Some researchers think it could even prove helpful with schizophrenia and Alzheimer's disease.

EPO (pronounced EE-poe) seems to protect a variety of organs and tissues from harm, including the heart, the brain and nervous system.

"We're very excited about it because it has widespread and very potent activity," said neuroscientist Michael Brines, director of research at Warren Pharmaceuticals. The company is looking at EPO's ability to heal spinal cord and cardiac damage. Animals treated with the drug show "remarkable" recovery, Brines said.

EPO has been around for millions of years; it exists in a wide range of animals, including fish and humans. Three decades ago, in one of the first feats of genetic engineering, scientists created a synthetic version of the substance.

Since then, artificial EPO has become a popular medicine for increasing red blood cell levels in anemics. Because boosting these cells increases the amount of oxygen available to muscles and lungs, the drug has also been used by elite endurance athletes looking for an unfair advantage. Many national and international sports organizations have banned its use.

But in the past four years, researchers have realized that EPO can do much more. "It has a lot of potential in terms of preventing tissue death," said Johns Hopkins University cardiologist Gregg Semenza, who is studying EPO's effect on the heart. In studies of rats, it significantly decreased heart attack damage.

High hopes

Another Johns Hopkins cardiologist, Joshua Hare, is studying EPO in pigs, whose hearts more closely resemble humans'. The data isn't in yet, but based on others' work and his own rat study, Hare has high hopes.

"It could greatly reduce the size of a heart attack, and the amount of damage," he said.

Surprisingly, some researchers say the two companies that make EPO seem less than enthusiastic about the drug's possible new uses. They accuse the companies, Amgen and Ortho Biotech, of showing little interest in funding new EPO research - possibly because new studies could uncover side effects that would endanger the drug's multibillion-dollar sales as an anemia drug. Both companies deny that.

Another possible reason for this alleged indifference: Recent studies looking at EPO as a cancer treatment found evidence that the drug may harm those patients.

Ironically, it is EPO's status as an approved drug that excites many researchers. Because it has been widely used for decades, researchers and regulators already know that it is relatively safe. "The beauty of EPO is that it's really well tolerated," said Ehrenreich, who is studying the drug as a stroke treatment.

She has found that patients given EPO injections within eight hours of a stroke did significantly better than those given a placebo. The EPO group had less brain damage and retained more functional ability: Only 14 percent ended up in nursing homes, compared with about half the placebo patients.

Ehrenreich recently started a larger study, which will examine more than 500 patients. If that trial goes well, EPO has a good chance of being approved in Germany, and perhaps the European Union, as a stroke treatment, she said.

In stroke and heart attack, EPO seems to work via the same mechanism, by blocking a process known as programmed cell death.

After many kinds of injury, cells around the damaged area destroy themselves in a misguided effort to promote healing. Ironically, this secondary suicide, called apoptosis, often causes more damage than the original injury. Somehow, Semenza says, EPO shuts off the cellular and genetic signals that trigger cell death.

Scientists have had little success in finding ways to stop apoptosis in humans. If EPO can do this, it would be a "huge deal, a new approach to tissue damage in general," says Hare.

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