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Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles

[Image: see text] Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system that can cause loss of motor function and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments suppress the immune...

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Autores principales: Peine, Kevin J., Guerau-de-Arellano, Mireia, Lee, Priscilla, Kanthamneni, Naveen, Severin, Mary, Probst, G. Duane, Peng, Haiyan, Yang, Yuhong, Vangundy, Zachary, Papenfuss, Tracey L., Lovett-Racke, Amy E., Bachelder, Eric M., Ainslie, Kristy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993881/
https://www.ncbi.nlm.nih.gov/pubmed/24433027
http://dx.doi.org/10.1021/mp4005172
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author Peine, Kevin J.
Guerau-de-Arellano, Mireia
Lee, Priscilla
Kanthamneni, Naveen
Severin, Mary
Probst, G. Duane
Peng, Haiyan
Yang, Yuhong
Vangundy, Zachary
Papenfuss, Tracey L.
Lovett-Racke, Amy E.
Bachelder, Eric M.
Ainslie, Kristy M.
author_facet Peine, Kevin J.
Guerau-de-Arellano, Mireia
Lee, Priscilla
Kanthamneni, Naveen
Severin, Mary
Probst, G. Duane
Peng, Haiyan
Yang, Yuhong
Vangundy, Zachary
Papenfuss, Tracey L.
Lovett-Racke, Amy E.
Bachelder, Eric M.
Ainslie, Kristy M.
author_sort Peine, Kevin J.
collection PubMed
description [Image: see text] Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system that can cause loss of motor function and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments suppress the immune system without antigen specificity, increasing the risks of cancer, chronic infection, and other long-term side effects. In this study, we show treatment of experimental autoimmune encephalomyelitis (EAE), a model of MS, by coencapsulating the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM) into acetalated dextran (Ac-DEX) microparticles (DXM/MOG/MPs) and administering the microparticles subcutaneously. The clinical score of the mice was reduced from 3.4 to 1.6 after 3 injections 3 days apart with the coencapsulated microparticulate formulation (MOG 17.6 μg and DXM 8 μg). This change in clinical score was significantly greater than observed with phosphate-buffered saline (PBS), empty MPs, free DXM and MOG, DXM/MPs, and MOG/MPs. Additionally, treatment with DXM/MOG/MPs significantly inhibited disease-associated cytokine (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we show a promising approach for the therapeutic treatment of MS using a polymer-based microparticle delivery platform.
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spelling pubmed-39938812015-01-16 Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles Peine, Kevin J. Guerau-de-Arellano, Mireia Lee, Priscilla Kanthamneni, Naveen Severin, Mary Probst, G. Duane Peng, Haiyan Yang, Yuhong Vangundy, Zachary Papenfuss, Tracey L. Lovett-Racke, Amy E. Bachelder, Eric M. Ainslie, Kristy M. Mol Pharm [Image: see text] Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system that can cause loss of motor function and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments suppress the immune system without antigen specificity, increasing the risks of cancer, chronic infection, and other long-term side effects. In this study, we show treatment of experimental autoimmune encephalomyelitis (EAE), a model of MS, by coencapsulating the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM) into acetalated dextran (Ac-DEX) microparticles (DXM/MOG/MPs) and administering the microparticles subcutaneously. The clinical score of the mice was reduced from 3.4 to 1.6 after 3 injections 3 days apart with the coencapsulated microparticulate formulation (MOG 17.6 μg and DXM 8 μg). This change in clinical score was significantly greater than observed with phosphate-buffered saline (PBS), empty MPs, free DXM and MOG, DXM/MPs, and MOG/MPs. Additionally, treatment with DXM/MOG/MPs significantly inhibited disease-associated cytokine (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we show a promising approach for the therapeutic treatment of MS using a polymer-based microparticle delivery platform. American Chemical Society 2014-01-16 2014-03-03 /pmc/articles/PMC3993881/ /pubmed/24433027 http://dx.doi.org/10.1021/mp4005172 Text en Copyright © 2014 American Chemical Society
spellingShingle Peine, Kevin J.
Guerau-de-Arellano, Mireia
Lee, Priscilla
Kanthamneni, Naveen
Severin, Mary
Probst, G. Duane
Peng, Haiyan
Yang, Yuhong
Vangundy, Zachary
Papenfuss, Tracey L.
Lovett-Racke, Amy E.
Bachelder, Eric M.
Ainslie, Kristy M.
Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title_full Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title_fullStr Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title_full_unstemmed Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title_short Treatment of Experimental Autoimmune Encephalomyelitis by Codelivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles
title_sort treatment of experimental autoimmune encephalomyelitis by codelivery of disease associated peptide and dexamethasone in acetalated dextran microparticles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993881/
https://www.ncbi.nlm.nih.gov/pubmed/24433027
http://dx.doi.org/10.1021/mp4005172
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