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New Version of Old Drug May Fight Brain Disease - 2004-07-10

Who says you can't teach an old drug new tricks? By making small changes to the chemical structure of the blood-building drug EPO, scientists have created a new version of the medicine that they hope can be used to treat many brain diseases.

Erythropoetin, known as EPO, is one of the top selling drugs in the world, with annual worldwide sales of about $9 billion. EPO is a protein that exists naturally in the body, but it is best known as a medicine used to help cancer patients and others increase their low blood counts. Some athletes have also used the blood-building drug illegally, to boost their energy.

Drug researcher Anthony Cerami, from Warren Pharmaceuticals in New York, a company that helped develop the drug, says that in addition to its blood-building effects, the drug can also stop damaged cells from dying and killing other healthy cells around them. EPO can help those damaged cells recover. Mr. Cerami calls this "tissue protection."

"The amazing thing about this molecule is that it has a number of other biologic activities," he said. "It can protect tissues like the brain, the eye, and the heart from various kinds of damages."

But until recently, there has been a significant problem with using EPO for brain and heart diseases. The drug would increase the blood count in people who do not need those blood-building effects, a side effect that could cause dangerous blood clots or strokes, especially with long-term use.

In a new development, Mr. Cerami, along with researchers in Denmark, Turkey and Italy, has now changed EPO slightly to make a new compound. The discovery of their new drug, which they call CEPO, is published in Science magazine. Mr. Cerami explains that the advantage of the new drug, CEPO, is that it has been modified so that it has only the tissue protective effects, without overproducing blood.

"What we've been able to do now, which is what this paper describes, is that we can modify EPO to make it a derivative which when you give it to animals, you no longer cause an increase in red blood cell production, but you still retain all of the tissue-protecting activities," he said. "And that's important because if you just gave EPO to an individual, what you would find is you would have too many red blood cells and you could actually hurt the patient as a result of that."

Independent scientist Hannelore Ehrenriech studies EPO at the Max Planck Institute for Experimental Medicine in Germany and shares Mr. Cerami's excitement over the new version of EPO. She says it could be used to treat brain tissue injured by a number of different diseases, like AIDS, multiple sclerosis, encephalitis, schizophrenia, Alzheimer's, spinal cord trauma, or diabetes. However, Ms. Ehrenreich says there's more work to be done.

"It is a new compound that is very promising in animals," said Hannelore Ehrenriech. "It raises the hope that we have the key for treating neurodegenerative diseases in humans. The first thing that needs to be done is to see whether CEPO is tolerated by humans, whether it will cause any trouble, then if it is well-tolerated, one has to prove the concept of neuroprotection in humans also."

Because CEPO's close relative, EPO, has already been proven safe and is in use, scientists hope that CEPO's journey from the lab to the bedside will be easy. Mr. Cerami says clinical trials will take four years.

In Germany, Ms. Ehrenreich does not yet know how widely available CEPO will be to those who need it. In an accompanying article in Science, she calls on drug companies to continue to invest in EPO research and to make sure it will be affordable.