New agents that stimulate erythropoiesis.

Recombinant human erythropoietin (rhEpo) has proven to be remarkably safe and effective for treatment of anemias, primarily those secondary to renal disease and malignancy. Despite the worldwide use of rhEpo, concerns about its cost, the need for frequent parenteral administration, and the development of anti-Epo antibodies have prompted development of improved agents to stimulate erythropoiesis. Three strategies appear to be particularly promising. The half-life of Epo in the circulation can be prolonged by the addition of N-linked carbohydrate groups, by formation of adducts with polyethylene glycol, and by preparation of Epo multimers. Second, mimetic peptides can effectively trigger signal transduction at the Epo receptor, thereby boosting red-cell production. Finally, the hypoxia inducible transcription factor (HIF) can be pharmacologically induced by oral agents, resulting in enhanced expression not only of endogenous Epo but also of other genes important in the regulation of erythropoiesis.