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Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis
Background: Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant my...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954767/ https://www.ncbi.nlm.nih.gov/pubmed/36831209 http://dx.doi.org/10.3390/cells12040542 |
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author | Koc, Ümmügülsüm Haupeltshofer, Steffen Klöster, Katharina Demir, Seray Gold, Ralf Faissner, Simon |
author_facet | Koc, Ümmügülsüm Haupeltshofer, Steffen Klöster, Katharina Demir, Seray Gold, Ralf Faissner, Simon |
author_sort | Koc, Ümmügülsüm |
collection | PubMed |
description | Background: Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant myelin oligodendrocyte glycoprotein(35-55) reactive T and B cells, mimicks features of chronic inflammation and degeneration in MS and related disorders. Here, we investigated the effects of prophylactic GA treatment on the clinical course, histological alterations and peripheral immune cells in OSE. Objective: To investigate the effects of prophylactic glatiramer acetate (GA) treatment in a mouse model of spontaneous opticospinal encephalomyelitis (OSE). Methods: OSE mice with a postnatal age of 21 to 28 days without signs of encephalomyelitis were treated once daily either with 150 µg GA or vehicle intraperitoneally (i. p.). The animals were scored daily regarding clinical signs and weight. The animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. We performed immunohistochemistry of spinal cord sections and flow cytometry analysis of immune cells. Results: Preventive treatment with 150 µg GA i. p. once daily significantly reduced clinical disease progression with a mean score of 3.9 ± 1.0 compared to 6.2 ± 0.7 in control animals (p < 0.01) after 30 d in accordance with positive effects on weight (p < 0.001). The immunohistochemistry showed that general inflammation, demyelination or CD11c(+) dendritic cell infiltration did not differ. There was, however, a modest reduction of the Iba1(+) area (p < 0.05) and F4/80(+) area upon GA treatment (p < 0.05). The immune cell composition of secondary lymphoid organs showed a trend towards an upregulation of regulatory T cells, which lacked significance. Conclusions: Preventive treatment with GA reduces disease progression in OSE in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with a high risk of disability, our study could provide valuable indications for translational medicine. |
format | Online Article Text |
id | pubmed-9954767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99547672023-02-25 Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis Koc, Ümmügülsüm Haupeltshofer, Steffen Klöster, Katharina Demir, Seray Gold, Ralf Faissner, Simon Cells Article Background: Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant myelin oligodendrocyte glycoprotein(35-55) reactive T and B cells, mimicks features of chronic inflammation and degeneration in MS and related disorders. Here, we investigated the effects of prophylactic GA treatment on the clinical course, histological alterations and peripheral immune cells in OSE. Objective: To investigate the effects of prophylactic glatiramer acetate (GA) treatment in a mouse model of spontaneous opticospinal encephalomyelitis (OSE). Methods: OSE mice with a postnatal age of 21 to 28 days without signs of encephalomyelitis were treated once daily either with 150 µg GA or vehicle intraperitoneally (i. p.). The animals were scored daily regarding clinical signs and weight. The animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. We performed immunohistochemistry of spinal cord sections and flow cytometry analysis of immune cells. Results: Preventive treatment with 150 µg GA i. p. once daily significantly reduced clinical disease progression with a mean score of 3.9 ± 1.0 compared to 6.2 ± 0.7 in control animals (p < 0.01) after 30 d in accordance with positive effects on weight (p < 0.001). The immunohistochemistry showed that general inflammation, demyelination or CD11c(+) dendritic cell infiltration did not differ. There was, however, a modest reduction of the Iba1(+) area (p < 0.05) and F4/80(+) area upon GA treatment (p < 0.05). The immune cell composition of secondary lymphoid organs showed a trend towards an upregulation of regulatory T cells, which lacked significance. Conclusions: Preventive treatment with GA reduces disease progression in OSE in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with a high risk of disability, our study could provide valuable indications for translational medicine. MDPI 2023-02-08 /pmc/articles/PMC9954767/ /pubmed/36831209 http://dx.doi.org/10.3390/cells12040542 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Koc, Ümmügülsüm Haupeltshofer, Steffen Klöster, Katharina Demir, Seray Gold, Ralf Faissner, Simon Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title | Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title_full | Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title_fullStr | Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title_full_unstemmed | Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title_short | Prophylactic Glatiramer Acetate Treatment Positively Attenuates Spontaneous Opticospinal Encephalomyelitis |
title_sort | prophylactic glatiramer acetate treatment positively attenuates spontaneous opticospinal encephalomyelitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954767/ https://www.ncbi.nlm.nih.gov/pubmed/36831209 http://dx.doi.org/10.3390/cells12040542 |
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