A single injection of liposomal asialo-erythropoietin improves motor function deficit caused by cerebral ischemia/reperfusion

Ishii, Takayuki; Asai, Tomohiro; Fukuta, Tatsuya; Oyama, Dai; Yasuda, Nodoka; Agato, Yurika; Shimizu, Kosuke; Minamino, Tetsuo; Oku, Naoto

doi:10.1016/j.ijpharm.2012.09.026

Cited by 35 publications

(27 citation statements)

References 28 publications

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“…Moreover, when liposomes were associated with contrast agents, researchers observed that they quickly accumulated in the ischemic zone. 134,143,148,152,190 Some formulations have demonstrated their ability to improve in vivo activity of drugs, such as chrysophanol, 133 dexamethasone phosphate, 154 nerve growth factor, 170 Xe, 150,158 FK506, 149 isopropylidene-shikimic acid, 151 asialo-erythropoietin, 153 antisense oligonucleotides, 165 plasmids, 174 quercetin, 166,168 fasudil, 176 nitric oxide, 146 N-acetylleucyl-leucyl-norleucine amide, 178 and a combination of synergistic drugs. 156,175 Very recently, a promising uncoupling new drug -ZL006 (5-(3, 5-dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid) -was developed for stroke treatment.…”

Section: Stroke or Cerebral Ischemiamentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

356

238

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This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

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Section: Stroke or Cerebral Ischemiamentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

356

238

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“…Recombinant hEPO produced in CHO (Chinese hamster ovary) cells is used for prevention or treatment of anaemia in nephrology and oncology patients, and can be abused for illegal doping activities. A glyco-engineered version of EPO (asialo-EPO) has no hematopoietic activity but can serve as a safe drug with neuro- and tissue-protective functions after stroke and additional hypoxia stress3536. Production of correctly N-glycosylated asialo-EPO in the moss bioreactor was reported recently6.…”

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confidence: 99%

A gene responsible for prolyl-hydroxylation of moss-produced recombinant human erythropoietin

Parsons

Altmann

Graf

et al. 2013

Sci Rep

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Recombinant production of pharmaceutical proteins is crucial, not only for personalized medicine. While most biopharmaceuticals are currently produced in mammalian cell culture, plant-made pharmaceuticals gain momentum. Post-translational modifications in plants are similar to those in humans, however, existing differences may affect quality, safety and efficacy of the products. A frequent modification in higher eukaryotes is prolyl-4-hydroxylase (P4H)-catalysed prolyl-hydroxylation. P4H sequence recognition sites on target proteins differ between humans and plants leading to non-human posttranslational modifications of recombinant human proteins produced in plants. The resulting hydroxyprolines display the anchor for plant-specific O-glycosylation, which bears immunogenic potential for patients. Here we describe the identification of a plant gene responsible for non-human prolyl-hydroxylation of human erythropoietin (hEPO) recombinantly produced in plant (moss) bioreactors. Targeted ablation of this gene abolished undesired prolyl-hydroxylation of hEPO and thus paves the way for plant-made pharmaceuticals humanized via glyco-engineering in moss bioreactors.

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“…In familial amyloidotic polyneuropathy, depressed levels of EPO may be associated with increased oxidative stress and apoptotic cell injury (358). EPO can prevent apoptotic injury against advanced glycation end-product (AGE) exposure in Schwann cells (359), sepsis (229, 360), cerebral ischemia (313, 345, 361), Aβ toxicity (186, 218, 358, 362–364), neuronal kainate-induced oxidative stress (26), vascular oxygen-glucose deprivation (194, 221, 310), hypoxia and anoxia (199, 365, 366), retinal disease (367, 368), experimental models of diabetes mellitus (194, 204, 314, 316, 369, 370), and toxins that destroy microglial cells (146, 166, 186, 227, 368). …”

Section: Erythropoietin and Programmed Cell Deathmentioning

confidence: 99%

Regeneration in the nervous system with erythropoietin

Maiese¹

2016

Front Biosci

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Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.

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A single injection of liposomal asialo-erythropoietin improves motor function deficit caused by cerebral ischemia/reperfusion

Cited by 35 publications

References 28 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

A gene responsible for prolyl-hydroxylation of moss-produced recombinant human erythropoietin

Regeneration in the nervous system with erythropoietin

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A single injection of liposomal asialo-erythropoietin improves motor function deficit caused by cerebral ischemia/reperfusion

Cited by 35 publications

References 28 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

A gene responsible for prolyl-hydroxylation of moss-produced recombinant human erythropoietin

Regeneration in the nervous system with erythropoietin

Contact Info

Product

Resources

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Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier