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Old Drug Learns New Tricks

Anemia medication altered to treat many other disorders

FRIDAY, July 9, 2004 (HealthDayNews) -- A slight alteration could turn a lone drug soldiering against one disease into a battalion able to combat a host of other disorders.

The drug in question, erythropoietin (EPO), is commonly used to treat anemia. But by making an ever-so-small tweak in its structure, researchers say, it can potentially be used to treat spinal cord injuries, heart failure, diabetes complications, and multiple sclerosis -- without any concern over EPO's known blood-clotting side effects.

That's the conclusion of a new study by a worldwide team of researchers appearing in the July 9 issue of Science.

In the study, the researchers reported that by changing one amino acid in the makeup of erythropoietin, the drug no longer boosts red blood cell production but still protects tissues in the body from damage.

With erythropoietin, "there's the potential of having a way to treat a number of diseases that are currently without therapy," said one of the study's authors, Anthony Cerami, the CEO of Warren Pharmaceuticals, which is developing the altered drug. Cerami, a former dean at Rockefeller University and a member of the National Academy of Sciences, conducted the research with scientists from Turkey, Italy, Denmark and the United States.

Erythropoietin is made primarily in the kidneys, according to Cerami. From the kidneys, it travels to the bone marrow, where it stimulates red blood cell production. In people with severe kidney disease, such as those requiring dialysis, the kidneys often can't produce enough erythropoietin, and severe anemia can occur if they don't take synthetic erythropoietin.

Red blood cell production, however, isn't erythropoietin's only function. It's also essential for protecting tissue damage after trauma, oxygen deprivation, or a challenge to the immune system, such as a bacterial infection.

That's because your immune system immediately recognizes such incidents as an invasion and starts to destroy all of the tissue that surrounds the damage. Erythropoietin is the substance the body produces to stop that cell destruction and limit the damage, according to Cerami.

So, if someone were having a stroke, administering additional erythropoietin could theoretically limit the damage done to the oxygen starved brain tissue.

Currently, however, when EPO is administered, it also increases the production of red blood cells. That's a problem because "it drives up your blood viscosity and can lead to thrombotic [blood clots] complications," explained Dr. Edward Amorosi, a hematologist at New York University Medical Center in New York City.

The challenge was for the researchers to find a way to turn off the red cell-boosting portion of erythropoietin.

"One of the things we wanted was to be able to have a molecule, which would not have the effect of increased red cells," said Cerami.

And, by using a process called carbamylating, that's exactly what they were able to do. They dubbed the new substance carbamylated erythropoietin (CEPO).

The change, said Cerami, is so simple and so small that if you compared pictures of the two molecules, you wouldn't notice it. But the simple change blocks the synthetic erythropoietin from binding to its receptor in the bone marrow so it doesn't induce red blood cell production.

"Now, we can have tissue-protecting activity without the increase in red blood cells," said Cerami.

In the Science study, the researchers report successful tests of CEPO for such diverse disorders as stroke, spinal cord injury, multiple sclerosis, and diabetic retinopathy in tissue cultures and in animal models.

"When used in experimental systems like tissue cultures and animal models of stroke, spinal cord injury, and demylinating disorders like MS, CEPO demonstrated some protective effect," said Amorosi.

Cerami said that EPO has few side effects and that its most significant complication comes from blood clotting, which shouldn't be a problem in CEPO, so they expect the new compound will be well-tolerated.

Cerami added that the researchers hope to move CEPO into clinical trials soon.

More information

To learn more about erythropoietin, visit the National Library of Medicine.

SOURCES: Anthony Cerami, Ph.D., CEO, Warren Pharmaceuticals, Ossining, N.Y.; Edward Amorosi, M.D., hematologist, New York University Medical Center, and associate professor of clinical medicine, New York University School of Medicine, New York; July 9, 2004, Science
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