Unexpected additive effects of minocycline and hydroxychloroquine in models of multiple sclerosis : Prospective combination treatment for progressive disease?
(2018) In Multiple Sclerosis Journal 24(12). p.1543-1556- Abstract
Background: Most multiple sclerosis (MS) patients succumb to a progressive phenotype. Continued lymphocyte activity in the brain, microglia-mediated injury, iron deposition, and oxidative stress are characteristics of progressive MS. Objective: As minocycline and hydroxychloroquine have been shown to inhibit microglia, we evaluated their effects on other outcomes relevant for progression. Methods: Medications were evaluated in culture and in mice with acute and chronic experimental autoimmune encephalomyelitis (EAE). Results: Both medications individually reduced iron neurotoxicity and a combination effect was not observed. Hydroxyl radical scavenging activity was manifested by minocycline only. Minocycline reduced T-cell proliferation... (More)
Background: Most multiple sclerosis (MS) patients succumb to a progressive phenotype. Continued lymphocyte activity in the brain, microglia-mediated injury, iron deposition, and oxidative stress are characteristics of progressive MS. Objective: As minocycline and hydroxychloroquine have been shown to inhibit microglia, we evaluated their effects on other outcomes relevant for progression. Methods: Medications were evaluated in culture and in mice with acute and chronic experimental autoimmune encephalomyelitis (EAE). Results: Both medications individually reduced iron neurotoxicity and a combination effect was not observed. Hydroxyl radical scavenging activity was manifested by minocycline only. Minocycline reduced T-cell proliferation more prominently than hydroxychloroquine; an aggregate effect occurred at low but not high concentrations. B-cell proliferation was mitigated to a greater extent by hydroxychloroquine and an additive effect was not evident. In EAE, suboptimal doses of minocycline and hydroxychloroquine individually delayed onset of clinical signs, while their combination suppressed clinical manifestations until treatment was stopped. In Biozzi ABH mice, a model of progressive MS, the chronic phase was beneficially altered using the combination. Conclusion: While minocycline and hydroxychloroquine did not manifest additive effects in most culture assays, their combination at suboptimal doses in EAE unexpectedly exceeded their individual activity. Minocycline and hydroxychloroquine combined are candidate treatments for progressive MS.
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- author
- Faissner, Simon ; Mahjoub, Yasamin ; Mishra, Manoj ; Haupeltshofer, Steffen LU ; Hahn, Jennifer Nancy ; Gold, Ralf ; Koch, Marcus ; Metz, Luanne M. ; Ben-Hur, Tamir and Yong, V. Wee
- publishing date
- 2018-10-01
- type
- Contribution to journal
- publication status
- published
- keywords
- antioxidant, Generic medication, neuroprotection, progressive multiple sclerosis
- in
- Multiple Sclerosis Journal
- volume
- 24
- issue
- 12
- pages
- 1543 - 1556
- publisher
- SAGE Publications
- external identifiers
-
- scopus:85041045072
- ISSN
- 1352-4585
- DOI
- 10.1177/1352458517728811
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © The Author(s), 2017.
- id
- c57db2d6-06ca-49a6-a18b-c68d0480e4e6
- date added to LUP
- 2026-02-05 09:10:15
- date last changed
- 2026-02-05 09:11:19
@article{c57db2d6-06ca-49a6-a18b-c68d0480e4e6,
abstract = {{<p>Background: Most multiple sclerosis (MS) patients succumb to a progressive phenotype. Continued lymphocyte activity in the brain, microglia-mediated injury, iron deposition, and oxidative stress are characteristics of progressive MS. Objective: As minocycline and hydroxychloroquine have been shown to inhibit microglia, we evaluated their effects on other outcomes relevant for progression. Methods: Medications were evaluated in culture and in mice with acute and chronic experimental autoimmune encephalomyelitis (EAE). Results: Both medications individually reduced iron neurotoxicity and a combination effect was not observed. Hydroxyl radical scavenging activity was manifested by minocycline only. Minocycline reduced T-cell proliferation more prominently than hydroxychloroquine; an aggregate effect occurred at low but not high concentrations. B-cell proliferation was mitigated to a greater extent by hydroxychloroquine and an additive effect was not evident. In EAE, suboptimal doses of minocycline and hydroxychloroquine individually delayed onset of clinical signs, while their combination suppressed clinical manifestations until treatment was stopped. In Biozzi ABH mice, a model of progressive MS, the chronic phase was beneficially altered using the combination. Conclusion: While minocycline and hydroxychloroquine did not manifest additive effects in most culture assays, their combination at suboptimal doses in EAE unexpectedly exceeded their individual activity. Minocycline and hydroxychloroquine combined are candidate treatments for progressive MS.</p>}},
author = {{Faissner, Simon and Mahjoub, Yasamin and Mishra, Manoj and Haupeltshofer, Steffen and Hahn, Jennifer Nancy and Gold, Ralf and Koch, Marcus and Metz, Luanne M. and Ben-Hur, Tamir and Yong, V. Wee}},
issn = {{1352-4585}},
keywords = {{antioxidant; Generic medication; neuroprotection; progressive multiple sclerosis}},
language = {{eng}},
month = {{10}},
number = {{12}},
pages = {{1543--1556}},
publisher = {{SAGE Publications}},
series = {{Multiple Sclerosis Journal}},
title = {{Unexpected additive effects of minocycline and hydroxychloroquine in models of multiple sclerosis : Prospective combination treatment for progressive disease?}},
url = {{http://dx.doi.org/10.1177/1352458517728811}},
doi = {{10.1177/1352458517728811}},
volume = {{24}},
year = {{2018}},
}