Weier, Alicia; Enders, Michael; Kirchner, Philipp; Ekici, Arif; Bigaud, Marc; Kapitza, Christopher; Wörl, Jürgen; Kuerten, Stefanie (2022). Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis. International journal of molecular sciences, 23(22) MDPI 10.3390/ijms232214209
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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Although immune modulation and suppression are effective during relapsing-remitting MS, secondary progressive MS (SPMS) requires neuroregenerative therapeutic options that act on the CNS. The sphingosine-1-phosphate receptor modulator siponimod is the only approved drug for SPMS. In the pivotal trial, siponimod reduced disease progression and brain atrophy compared with placebo. The enteric nervous system (ENS) was recently identified as an additional autoimmune target in MS. We investigated the effects of siponimod on the ENS and CNS in the experimental autoimmune encephalomyelitis model of MS. Mice with late-stage disease were treated with siponimod, fingolimod, or sham. The clinical disease was monitored daily, and treatment success was verified using mass spectrometry and flow cytometry, which revealed peripheral lymphopenia in siponimod- and fingolimod-treated mice. We evaluated the mRNA expression, ultrastructure, and histopathology of the ENS and CNS. Single-cell RNA sequencing revealed an upregulation of proinflammatory genes in spinal cord astrocytes and ependymal cells in siponimod-treated mice. However, differences in CNS and ENS histopathology and ultrastructural pathology between the treatment groups were absent. Thus, our data suggest that siponimod and fingolimod act on the peripheral immune system and do not have pronounced direct neuroprotective effects.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Kirchner, Paul Philipp |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1422-0067 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
28 Nov 2022 12:27 |
Last Modified: |
05 Dec 2022 16:29 |
Publisher DOI: |
10.3390/ijms232214209 |
PubMed ID: |
36430692 |
Uncontrolled Keywords: |
central nervous system enteric nervous system experimental autoimmune encephalomyelitis fingolimod multiple sclerosis siponimod |
BORIS DOI: |
10.48350/175192 |
URI: |
https://boris.unibe.ch/id/eprint/175192 |
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