Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis

Weier A, Enders M, Kirchner P, Ekici AB, Bigaud M, Kapitza C, Wörl J, Kuerten S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 23

Article Number: 14209

Journal Issue: 22

DOI: 10.3390/ijms232214209

Abstract

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.

Authors with CRIS profile

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Universität Bern Switzerland (CH) Novartis AG Switzerland (CH)

How to cite

APA:

Weier, A., Enders, M., Kirchner, P., Ekici, A.B., Bigaud, M., Kapitza, C.,... Kuerten, S. (2022). Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis. International Journal of Molecular Sciences, 23(22). https://doi.org/10.3390/ijms232214209

MLA:

Weier, Alicia, et al. "Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis." International Journal of Molecular Sciences 23.22 (2022).

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