NIH News Release
National Institute of Diabetes and
Digestive and Kidney Diseases

Tuesday, March 3, 1998

Mary Harris
(301) 435-8114
Jane DeMouy
(301) 435-8115

Researchers Identify Potential New Drug Treatment for Iron Overload
Cooley's Anemia and Sickle Cell Patients Would Benefit

Researchers may have found a better drug treatment to remove iron from patients who have too much. Too much iron damages vital organs, especially the liver, heart, and pancreas. That's a problem for as many as 50,000 people in the United States who need regular blood transfusions for anemias such as Cooley's anemia and some patients with sickle cell disease.

The small intestine usually regulates how much iron is absorbed into the blood, but transfusions bypass this safety mechanism, sending iron-rich blood straight to the bloodstream. To rid the body of extra iron, patients use a chelator, a drug that attaches to iron so it can escape body cells and be excreted in stool and urine. Unfortunately, the standard chelator, deferoxamine (DFO), is expensive and has effects patients don't like.

The drug, HBED or hydroxybenzylethylenediamine diacetic acid, removed up to 3 times more iron than DFO when tested in normal rats and in primates overloaded with iron. The study appears in the February 15 issue of Blood and was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases.

"We've been desperate to offer something better to patients," said Raymond J. Bergeron, Ph.D., lead author of the study and a medicinal chemist at the University of Florida College of Pharmacy in Gainesville. "We don't want to raise false hopes before we've done more studies, but primates are a magnificent predictor of what will happen in people, and this looks great in the primate. It's hard not to get excited," said Bergeron.

For years researchers have been searching for an oral alternative to DFO. "Considering it's given almost every day over people's lifetimes, DFO is really remarkably free of side effects," said Gary Brittenham, M.D., a hematologist at Case Western Reserve University and coauthor of the Blood study. However, patients must inject it for 9 to 12 hours at least 5 days a week and most get red, swollen and painful skin around the injection site. The time involved and the localized reactions become so troublesome to patients over the long haul that some eventually refuse to use it as they should or at all. "It causes tremendous discomfort," said Bergeron.

HBED still must be injected under the skin, but the researchers are hopeful that its increased effectiveness over DFO will mean that one quick injection two or three times a week will do the job. Because HBED is synthetic it will be not only cheaper to produce but also less likely to provoke allergic responses, increasing patients' willingness to use the drug.

The researchers already have begun running HBED through the first of a series of progressively larger and longer studies to test the drug again in rats, in dogs, and in humans, possibly by Fall. If all goes well, Brittenham predicted that HBED might be available for widespread use in 3 to 5 years.

HBED has potential application to other conditions as well. "Iron chelators have documented anti-malarial properties," a disease in need of alternatives, according to Brittenham. "The situation is almost desperate now because malarial parasites have become resistant to almost every drug." Brittenham proposed that iron chelators might also be useful in treating inflammatory diseases such as inflammatory bowel disease and some forms of heart disease.

Note: The National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute also funded this research.