Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment
Neuroprotective drugs to protect the brain against cerebral ischemia and reperfusion (I/R) injury are urgently needed. Mammalian cell-produced recombinant human erythropoietin (rhuEPO<sup>M</sup>) has been demonstrated to have excellent neuroprotective functions in preclinical studies, b...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/4/610 |
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| author | Farooqahmed S. Kittur Chiu-Yueh Hung P. Andy Li David C. Sane Jiahua Xie |
| author_facet | Farooqahmed S. Kittur Chiu-Yueh Hung P. Andy Li David C. Sane Jiahua Xie |
| author_sort | Farooqahmed S. Kittur |
| collection | DOAJ |
| description | Neuroprotective drugs to protect the brain against cerebral ischemia and reperfusion (I/R) injury are urgently needed. Mammalian cell-produced recombinant human erythropoietin (rhuEPO<sup>M</sup>) has been demonstrated to have excellent neuroprotective functions in preclinical studies, but its neuroprotective properties could not be consistently translated in clinical trials. The clinical failure of rhuEPO<sup>M</sup> was thought to be mainly due to its erythropoietic activity-associated side effects. To exploit its tissue-protective property, various EPO derivatives with tissue-protective function only have been developed. Among them, asialo-rhuEPO, lacking terminal sialic acid residues, was shown to be neuroprotective but non-erythropoietic. Asialo-rhuEPO can be prepared by enzymatic removal of sialic acid residues from rhuEPO<sup>M</sup> (asialo-rhuEPO<sup>E</sup>) or by expressing human <i>EPO</i> gene in glycoengineered transgenic plants (asialo-rhuEPO<sup>P</sup>). Both types of asialo-rhuEPO, like rhuEPO<sup>M</sup>, displayed excellent neuroprotective effects by regulating multiple cellular pathways in cerebral I/R animal models. In this review, we describe the structure and properties of EPO and asialo-rhuEPO, summarize the progress on neuroprotective studies of asialo-rhuEPO and rhuEPO<sup>M</sup>, discuss potential reasons for the clinical failure of rhuEPO<sup>M</sup> with acute ischemic stroke patients, and advocate future studies needed to develop asialo-rhuEPO as a multimodal neuroprotectant for ischemic stroke treatment. |
| first_indexed | 2024-03-11T04:38:34Z |
| format | Article |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T04:38:34Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-bd627d199349486982072b72704b4b422023-11-17T20:51:22ZengMDPI AGPharmaceuticals1424-82472023-04-0116461010.3390/ph16040610Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke TreatmentFarooqahmed S. Kittur0Chiu-Yueh Hung1P. Andy Li2David C. Sane3Jiahua Xie4Department of Pharmaceutical Sciences, Biomanufacturing Research Institute & Technology Enterprise, North Carolina Central University, Durham, NC 27707, USADepartment of Pharmaceutical Sciences, Biomanufacturing Research Institute & Technology Enterprise, North Carolina Central University, Durham, NC 27707, USADepartment of Pharmaceutical Sciences, Biomanufacturing Research Institute & Technology Enterprise, North Carolina Central University, Durham, NC 27707, USACarilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, VA 24014, USADepartment of Pharmaceutical Sciences, Biomanufacturing Research Institute & Technology Enterprise, North Carolina Central University, Durham, NC 27707, USANeuroprotective drugs to protect the brain against cerebral ischemia and reperfusion (I/R) injury are urgently needed. Mammalian cell-produced recombinant human erythropoietin (rhuEPO<sup>M</sup>) has been demonstrated to have excellent neuroprotective functions in preclinical studies, but its neuroprotective properties could not be consistently translated in clinical trials. The clinical failure of rhuEPO<sup>M</sup> was thought to be mainly due to its erythropoietic activity-associated side effects. To exploit its tissue-protective property, various EPO derivatives with tissue-protective function only have been developed. Among them, asialo-rhuEPO, lacking terminal sialic acid residues, was shown to be neuroprotective but non-erythropoietic. Asialo-rhuEPO can be prepared by enzymatic removal of sialic acid residues from rhuEPO<sup>M</sup> (asialo-rhuEPO<sup>E</sup>) or by expressing human <i>EPO</i> gene in glycoengineered transgenic plants (asialo-rhuEPO<sup>P</sup>). Both types of asialo-rhuEPO, like rhuEPO<sup>M</sup>, displayed excellent neuroprotective effects by regulating multiple cellular pathways in cerebral I/R animal models. In this review, we describe the structure and properties of EPO and asialo-rhuEPO, summarize the progress on neuroprotective studies of asialo-rhuEPO and rhuEPO<sup>M</sup>, discuss potential reasons for the clinical failure of rhuEPO<sup>M</sup> with acute ischemic stroke patients, and advocate future studies needed to develop asialo-rhuEPO as a multimodal neuroprotectant for ischemic stroke treatment.https://www.mdpi.com/1424-8247/16/4/610multimodal neuroprotectanterythropoietinhematopoietic activityasialo-erythropoietinnon-erythropoiesiserythropoietin receptor |
| spellingShingle | Farooqahmed S. Kittur Chiu-Yueh Hung P. Andy Li David C. Sane Jiahua Xie Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment Pharmaceuticals multimodal neuroprotectant erythropoietin hematopoietic activity asialo-erythropoietin non-erythropoiesis erythropoietin receptor |
| title | Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment |
| title_full | Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment |
| title_fullStr | Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment |
| title_full_unstemmed | Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment |
| title_short | Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment |
| title_sort | asialo rhuepo as a potential neuroprotectant for ischemic stroke treatment |
| topic | multimodal neuroprotectant erythropoietin hematopoietic activity asialo-erythropoietin non-erythropoiesis erythropoietin receptor |
| url | https://www.mdpi.com/1424-8247/16/4/610 |
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