NEW YORK (Reuters Health) - A derivative of erythropoietin (EPO), known as carbamylated EPO, seems to provide all the cardioprotection of the parent compound without some of the undesirable effects, such as thrombogenesis, findings from an animal study indicate.
The identification of carbamylated EPO as a potentially useful cardioprotective agent came when Dr. Michael Brines, from the Kenneth S. Warren Institute in Ossining, New York, and colleagues began investigating the mechanisms behind EPO’s cardiac effects.
While it has been shown that EPO can protect the heart from ischemic injury, it was unclear if this was due to its well-known hemoglobin-raising effect or to its ability to prevent cardiomyocyte apoptosis. To investigate, the researchers used a rat model of myocardial infarction to analyze the effects of carbamylated EPO, which unlike the parent compound does not stimulate the EPO receptor and increase hemoglobin levels.
The findings appear in the January 24th early edition of the Proceedings of the National Academy of Sciences.
“Carbamylated EPO protected the heart to virtually the same extent as regular EPO,” suggesting that anti-apoptotic effects are largely responsible for EPO’s cardiac benefits, Dr. Brines told Reuters Health.
In vivo, treatment with carbamylated EPO just before reperfusion was associated with a significant reduction in cardiomyocyte loss. In vitro, exposure to the derivative significantly reduced cardiomyocyte apoptosis.
“By activating platelets, EPO causes blood-clotting, which is worrisome in the setting of heart injury,” Dr. Brines noted. By contrast, “carbamylated EPO and other derivatives don’t have this effect.”
“We’re hoping that phase I trials [of these EPO analogs] will begin within the next year,” Dr. Brines said. If these agents perform well in human trials, the approval process might be accelerated since the parent compound is already approved, he added.
Source: Proc Natl Acad Sci USA 2005. [ Google search on this article ]
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