Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

A novel substrate based on electrospun polyurethane nanofibers and electrosprayed polyvinyl alcohol microparticles for recombinant human erythropoietin delivery.

After myocardial infarction caused by a heart attack, endothelial cells need to be preserved in order to regenerate new capillaries. Moreover, sufficient mechanical support is necessary for the infarcted myocardium to pump the blood. Herein, we designed a novel substrate containing polyurethane (PU) nanofibrous layers and recombinant human erythropoietin (rhEPO)-loaded microparticles for both controlled releases of rhEPO and mechanical support of myocardium. In this system, the single-layer (SL) and double-layer (DL) PU nanofibers were electrospun, and then microparticles with different rhEPO:polyvinyl alcohol (PVA) ratios were electrosprayed on the layers. The in vitro release behavior of rhEPO from SL substrates was not satisfactory, and then the study focused on DL patches in which the release profile was in accordance with Korsmeyer-Peppas model. The release exponent of 0.89 for the DL PU/120PVA:1rhEPO represented zero-order release. The results inferred that these substrates possessed highly tailored mechanical properties; Young's modulus and ultimate tensile strength of the substrates were 74-172 kPa and 7.4-9.9 MPa, respectively. The rhEPO release from the substrates was leading to the proper adhesion of endothelial cells and more than 95% cell viability. The results indicated that the patch of elastic nanofibers and microparticles offered a potential substrate for simultaneous rhEPO delivery to endothelial cells and also mechanically supporting the infarcted myocardium.

Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach.

Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.

Asymptomatic late thrombocytosis is a common finding in very preterm infants even in the absence of erythropoietin treatment.

OBJECTIVES: Thrombocytosis is more prevalent in pediatric than in adult patients and is associated with complications or worsened outcomes after vascular events. This study aimed to determine the prevalence of thrombocytosis in very preterm infants who had not received human recombinant erythropoietin treatment (rHuEPO) and its relationship with other hematological parameters and clinical complications. METHODS: We performed a retrospective study of hematological and clinical data of very preterm infants who were admitted to our unit in their first 48 hours of life and stayed for longer than 1 week. RESULTS: Thrombocytosis was prevalent (32.6% of patients) in very preterm infants (≤32 weeks of gestational age, n = 193) who had not received rHuEPO. The platelet count was positively correlated with calendar age. Infants with thrombocytosis were significantly more premature (28.0 ± 2.1 versus 29.6 ± 2.2 weeks) and had a lower birth weight (1036 ± 304 versus 1303 ± 304) than those without thrombocytosis. Thrombocytosis was associated with retinopathy of prematurity after adjusting for gestational age and comorbidities, but not with other prematurity-associated complications. CONCLUSIONS: Late asymptomatic thrombocytosis is common in very preterm infants at approximately 1 month of postnatal age and it may be associated with retinopathy of prematurity.

Effects of recombinant human erythropoietin and bone marrow mesenchymal stem cell transplantation on renal inflammatory response following cardiopulmonary bypass in rats / 医学研究生学报

[Abstract ] Objective The aim of the study was to investigate the effects of recombinant human erythoropoietin (EPO) and bone marrow mesenchymal stem cell (BMSC) transplantation on renal inflammatory response following cardiopulmonary bypass (CPB). Methods Forty sprague-Dawley male rats were randomly divided into five groups (n=8):shame operation group, CPB group, EPO group, BMSC group and EPO +BMSC group.CPB model was built in shame operation group without CPB .The other four groups un-derwent CPB, following by jugular vein infusion of 1.5 ×106 BMSCs after an hour′s 100 L/kg/min bypass .Jugular vein infusion of 3000 IU/kg EPO was done in EPO group , while the combination of EPO with BMSCs was infused in EPO +BMSC group.The same volume of isotonic saline solution was infused via jugular vein in CPB group and shame operation group respectively .Rats were sacrificed at 24 hours after CPB termination .Blood samples were collected for the determi-nation of creatinine(Cr) and urea nitro(BUN) levels.HE staining was applied in the examination of renal tissues .ELISA was used in the determination of serum interleukin 6 (IL-6) and interleukin 10 (IL-10) levels and western blot was taken to test the expressions of tumor necrosis factor (TNF-α) and insulin-like growth factor 1 (IGF-1). Results In CPB group, the levels of Cr, BUN, IL-6 and the expression of TNF-αwere increased, while IL-10 level and of IGF-1 expression were decreased(P<0.05).TNF-αexpression was increased while IGF-1 expression was decreased in renal tissue (P<0.05).HE staining results showed the renal injury in EPO +BM-SC group was significantly lower than those in EPO group , BMSC group and CPB group , along with the decrease in the levels of Cr , BUN, IL-6, the increase in IL-10 level(P<0.05), as well as the decline of TNF-αexpression and the rise of IGF-1 expression(P<0.05). Conclusion The combination of EPO and BMSCs which reduces renal inflammatory response following CPB has protective effects on renal injury following CPB in rats , which is better than single application of EPO or BMSCs .

Eficacia y seguridad de la eritropoyetina en la anemia de la prematuridad / Efficacy and safety of erythropoietin for anemia of prematurity

Introducción: la eritropoyetina alfa recombinante forma parte del tratamiento de la anemia de la prematuridad. En Cuba su uso ha sido limitado y controvertido en cuanto a esquema y dosis empleada. Métodos: ensayo clínico prospectivo, multicéntrico, no aleatorizado, de eficacia y seguridad de eritropoyetina en la disminución de transfusiones en el recién nacido pretérmino de muy bajo peso. Se incluyeron 72 neonatos con edad gestacional menor de 34 semanas posmenstruales, y peso al nacer menor o igual a 1 500 g, con más de 7 días posnatales e ingesta de 50 mL/kg/día. Resultados: todos recibieron eritropoyetina 300 U/kg, subcutánea, 3 veces/semana, hasta las 40 semanas de edad gestacional y suplemento de hierro y vitaminas. La eritropoyetina fue muy segura, solo se notificó con relación posible una retinopatía de la prematuridad, ligera y recuperada. Conclusiones: se transfundieron 7 pacientes (9,7 por ciento) en el curso del estudio. El uso tardío de eritropoyetina en el pretérmino de muy bajo peso confirma su eficacia y seguridad

Introduction: recombinant alpha erythropoietin is part of the treatment for anemia of prematurity. The use of this one in Cuba has been restricted and controversial as to schedule and dose. Methods: prospective, non-randomized multicenter assay on the safety and efficacy of erythropoietin in the reduction of blood transfusion in very-low-weight preterm newborn. Seventy two neonates with gestational age under 34 post-menstruation weeks, weighing equal or less than 1 500 g, over 7 days of life after birth and fed on 50 mL/kg/day were included in the study. Results: all of them received 300 U/kg erythropoietin by subcutaneous administration three times a week up to reaching 40 weeks of gestational age and an iron and vitamin supplement. Erythropoietin is very safe; it was just possibly related to slight retinopathy of prematurity, but overcome. Conclusions: seven patients were transfused (9.7 percent ) in the course of study. The late use of erythropoietin in very-low-weight preterm child confirms its efficacy and safety

Eficacia y seguridad de la eritropoyetina en la anemia de la prematuridad / Efficacy and safety of erythropoietin for anemia of prematurity

Introducción: la eritropoyetina alfa recombinante forma parte del tratamiento de la anemia de la prematuridad. En Cuba su uso ha sido limitado y controvertido en cuanto a esquema y dosis empleada. Métodos: ensayo clínico prospectivo, multicéntrico, no aleatorizado, de eficacia y seguridad de eritropoyetina en la disminución de transfusiones en el recién nacido pretérmino de muy bajo peso. Se incluyeron 72 neonatos con edad gestacional menor de 34 semanas posmenstruales, y peso al nacer menor o igual a 1 500 g, con más de 7 días posnatales e ingesta de 50 mL/kg/día. Resultados: todos recibieron eritropoyetina 300 U/kg, subcutánea, 3 veces/semana, hasta las 40 semanas de edad gestacional y suplemento de hierro y vitaminas. La eritropoyetina fue muy segura, solo se notificó con relación posible una retinopatía de la prematuridad, ligera y recuperada. Conclusiones: se transfundieron 7 pacientes (9,7 por ciento) en el curso del estudio. El uso tardío de eritropoyetina en el pretérmino de muy bajo peso confirma su eficacia y seguridad(AU)

Introduction: recombinant alpha erythropoietin is part of the treatment for anemia of prematurity. The use of this one in Cuba has been restricted and controversial as to schedule and dose. Methods: prospective, non-randomized multicenter assay on the safety and efficacy of erythropoietin in the reduction of blood transfusion in very-low-weight preterm newborn. Seventy two neonates with gestational age under 34 post-menstruation weeks, weighing equal or less than 1 500 g, over 7 days of life after birth and fed on 50 mL/kg/day were included in the study. Results: all of them received 300 U/kg erythropoietin by subcutaneous administration three times a week up to reaching 40 weeks of gestational age and an iron and vitamin supplement. Erythropoietin is very safe; it was just possibly related to slight retinopathy of prematurity, but overcome. Conclusions: seven patients were transfused (9.7 percent ) in the course of study. The late use of erythropoietin in very-low-weight preterm child confirms its efficacy and safety(AU)