epoetin-alfa and Central-Nervous-System-Diseases

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury.

Topics: Anemia; Central Nervous System; Central Nervous System Diseases; Clinical Trials as Topic; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neuroprotective Agents; Recombinant Proteins