The role of erythropoietin in neuroprotection: therapeutic perspectives.
Nervous system diseases are very complex conditions comprising a large variety of local and systemic responses. Several therapeutic agents interfering with all or in part the biochemical steps that ultimately cause neuronal death have been demonstrated to be neuroprotective in preclinical models. However, all the agents so far investigated have inexorably failed in the phase III trials carried out. A large body of evidence suggests that the hormone erythropoietin (EPO), besides its well-known hematopoietic action, exerts beneficial effects in the central nervous system. EPO's effect has been assessed in several experimental models of brain and spinal cord injury thus becoming a serious candidate for neuroprotection. The use of EPO as neuroprotectant raises several questions. Besides dosage and therapeutic time window, the safety of recombinant EPO administration in the setting of nervous system diseases takes priority over all other questions. Although recombinant EPO seems to be potentially safe at the neuroprotective proved doses, cardiovascular or cerebrovascular events can occur as a result of its bone marrow stimulating activities. The successful trial using EPO in patients with ischemic stroke and the large body of experimental evidence encourages intensive evaluation of this cytokine to support safe and larger clinical trials in the near future.
Grasso
Giovanni
G
Department of Neurosurgery, University of Palermo, Palermo, Italy. Giovanni.Grasso@unipa.it
Sfacteria
Alessandra
A
Meli
Francesco
F
Passalacqua
Marcello
M
Fodale
Vincenzo
V
Buemi
Michele
M
Giambartino
Filippo
F
Iacopino
Domenico G
DG
Tomasello
Francesco
F
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins; D020521:Stroke / Q000378:metabolism / Q000517:prevention & control; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D020928:Mitogen-Activated Protein Kinases