NEW YORK (Reuters Health) - Scientists have created a derivative of erythropoietin - carbamylated erythropoietin - which they say has impressive neuroprotective effects but lacks the red blood cell-boosting effects of erythropoietin.
Recent studies showing that erythropoietin has potent neuroprotective properties in addition to its well-known erythropoietic effects (see Reuters Health reports Mar. 29, 2004 and Dec. 9, 2002) have fueled efforts to design a compound that would separate the two bioactivities.
Carbamylated erythropoietin seems to fit the bill, according to Dr. Marcel Leist from H. Lundbeck A/S in Valby, Denmark and colleagues. Carbamylated erythropoietin does not bind to the erythropoietin receptor, which mediates erythropoietin’s hematopoietic effects. It also had absolutely no hematopoietic activity in culture or upon chronic dosing in different animal species, they report in the July 9th issue of the journal Science.
On the other hand, carbamylated erythropoietin is cytoprotective in vitro and in rodents confers significant neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a magnitude similar to erythropoietin. Carbamylated erythropoietin also has a longer plasma half-life compared with other erythropoietin derivatives.
Carbamylated erythropoietin “has the potential to fundamentally alter current modes of therapy in a number of important diseases,” Dr. Anthony Cerami a co-author on the Science paper and CEO of Warren Pharmaceuticals, the company advancing carbamylated erythropoietin, told Reuters Health. “By separating the bone marrow activating function of erythropoietin from its tissue-protective function, we have been able to target only tissue injury.”
In an editorial, Dr. Hannelore Ehrenreich from the Max-Planck Institute for Experimental Medicine in Goettingen, Germany writes that “the fact that erythropoietin is safe and well-tolerated by millions of anemia patients holds promise that carbamylated erythropoietin can be rapidly moved to the clinic.”
“As clinicians continue to optimize neuroprotective treatment regimens for human patients, short-term, high-dose application of recombinant human erythropoietin for treating acute conditions like stroke may remain the strategy of choice,” the researcher writes.
In contrast, carbamylated erythropoietin “may be the preferred drug” for long-term treatment of patients with chronic neurological and psychiatric conditions in whom erythropoietin’s red blood cell-boosting effects would be undesirable, Dr. Ehrenreich adds.
Source: Science 2004. [ Google search on this article ]
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