The potential of erythropoietin and related strategies to stimulate erythropoiesis.

During the 15 years since the cloning of the erythropoietin (EPO) gene, the recombinant hormone has become an extraordinarily successful therapeutic for the treatment of renal and several nonrenal anemias. Considerable insight was gained into the adverse consequences of chronic reduction in hemoglobin levels on quality of life, physiological functions and survival. Precise cost-benefit relationships, however, are still lacking and target hemoglobin levels remain controversial. Nevertheless, given the wide application and potential of erythropoietic stimulation, there is growing interest in alternative but related strategies, including the development of second generation molecule EPO-mimetics, modulators of receptor activity and EPO gene therapy.