| Prevention of diabetic neuropathy by regulatable expression of HSV-mediated erythropoietin. | |
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MedLine Citation:
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PMID: 20924361 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have demonstrated that gene transfer of genes coding for neurotrophic factors to the dorsal root ganglion (DRG) using nonreplicating herpes simplex virus (HSV)-based vectors injected subcutaneously can prevent the progression of diabetic neuropathy. Because prolonged expression of neurotrophic factors could potentially have unwanted adverse effects, we constructed a nonreplicating HSV vector, vHrtEPO, to express erythropoietin (EPO) under the control of a tetracycline response element (TRE)-minimal cytomegalovirus (CMV) fusion promoter. Primary DRG neurons in culture infected with vHrtEPO express and release EPO in response to exposure to doxycycline (DOX). Animals infected with vHrtEPO by footpad inoculation demonstrated regulated expression of EPO in DRG under the control of DOX administered by gavage. Mice rendered diabetic by injection of streptozotocin (STZ), inoculated with vHrtEPO, and treated with DOX 4 days out of 7 each week for 4 weeks were protected against the development of diabetic neuropathy as assessed by electrophysiologic and behavioral measures. These studies indicate that intermittent expression of EPO in DRG achieved from a regulatable vector is sufficient to protect against the progression of neuropathy in diabetic animals, and provides proof-of-principle preclinical evidence for the development of such vectors for clinical trial. |
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Authors:
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Zetang Wu; Marina Mata; David J Fink |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-05 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: 19 ISSN: 1525-0024 ISO Abbreviation: Mol. Ther. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-03 Completed Date: 2011-05-11 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 310-7 Citation Subset: IM |
Affiliation:
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Department of Neurology, University of Michigan, Ann Arbor, MI, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Cercopithecus aethiops Diabetic Neuropathies / genetics, therapy* Electrophysiology Enzyme-Linked Immunosorbent Assay Erythropoietin / genetics, metabolism* Ganglia, Spinal / metabolism* Gene Therapy / methods* Genetic Vectors / genetics* Male Mice Nerve Growth Factors / genetics, physiology* Polymerase Chain Reaction Promoter Regions, Genetic / drug effects Rats Simplexvirus / genetics* Tetracycline / pharmacology Vero Cells |
| Grant Support | |
ID/Acronym/Agency:
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P01 DK044935-150001/DK/NIDDK NIH HHS; R01 NS038850-11/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nerve Growth Factors; 11096-26-7/Erythropoietin; 60-54-8/Tetracycline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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