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Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Overview of attention for article published in Journal of Neuroinflammation, August 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

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2 news outlets
blogs
1 blog
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4 X users
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3 patents

Citations

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128 Dimensions

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143 Mendeley
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Title
Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis
Published in
Journal of Neuroinflammation, August 2016
DOI 10.1186/s12974-016-0686-4
Pubmed ID
Authors

Antonietta Gentile, Alessandra Musella, Silvia Bullitta, Diego Fresegna, Francesca De Vito, Roberta Fantozzi, Eleonora Piras, Francesca Gargano, Giovanna Borsellino, Luca Battistini, Anna Schubart, Georgia Mandolesi, Diego Centonze

Abstract

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE. Minipumps allowing continuous intracerebroventricular (icv) infusion of siponimod for 4 weeks were implanted into C57BL/6 mice subjected to MOG35-55-induced EAE. Electrophysiology, immunohistochemistry, western blot, qPCR experiments, and peripheral lymphocyte counts were performed. In addition, the effect of siponimod on activated microglia was assessed in vitro to confirm the direct effect of the drug on CNS-resident immune cells. Siponimod administration (0.45 μg/day) induced a significant beneficial effect on EAE clinical scores with minimal effect on peripheral lymphocyte counts. Siponimod rescued defective GABAergic transmission in the striatum of EAE, without correcting the EAE-induced alterations of glutamatergic transmission. We observed a significant attenuation of astrogliosis and microgliosis together with reduced lymphocyte infiltration in the striatum of EAE mice treated with siponimod. Interestingly, siponimod reduced the release of IL-6 and RANTES from activated microglial cells in vitro, which might explain the reduced lymphocyte infiltration. Furthermore, the loss of parvalbumin-positive (PV+) GABAergic interneurons typical of EAE brains was rescued by siponimod treatment, providing a plausible explanation of the selective effects of this drug on inhibitory synaptic transmission. Altogether, our results show that siponimod has neuroprotective effects in the CNS of EAE mice, which are likely independent of its peripheral immune effect, suggesting that this drug could be effective in limiting neurodegenerative pathological processes in MS.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 143 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 <1%
Unknown 142 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 30 21%
Student > Master 19 13%
Student > Ph. D. Student 15 10%
Student > Bachelor 10 7%
Other 10 7%
Other 20 14%
Unknown 39 27%
Readers by discipline Count As %
Neuroscience 30 21%
Medicine and Dentistry 20 14%
Agricultural and Biological Sciences 13 9%
Biochemistry, Genetics and Molecular Biology 11 8%
Pharmacology, Toxicology and Pharmaceutical Science 11 8%
Other 13 9%
Unknown 45 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 37. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 September 2023.
All research outputs
#1,038,168
of 24,580,204 outputs
Outputs from Journal of Neuroinflammation
#83
of 2,840 outputs
Outputs of similar age
#19,495
of 345,637 outputs
Outputs of similar age from Journal of Neuroinflammation
#2
of 51 outputs
Altmetric has tracked 24,580,204 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,840 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has done particularly well, scoring higher than 97% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,637 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 51 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.