RGD Reference Report - Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection. - Rat Genome Database

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Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection.

Authors: Ambrosius, Björn  Pitarokoili, Kalliopi  Schrewe, Lisa  Pedreiturria, Xiomara  Motte, Jeremias  Gold, Ralf 
Citation: Ambrosius B, etal., J Neuroinflammation. 2017 Apr 26;14(1):92. doi: 10.1186/s12974-017-0864-z.
RGD ID: 13782060
Pubmed: PMID:28446186   (View Abstract at PubMed)
PMCID: PMC5406994   (View Article at PubMed Central)
DOI: DOI:10.1186/s12974-017-0864-z   (Journal Full-text)


BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor modulator with well-described immunomodulatory properties involving peripheral immune cell trafficking, was the first oral agent approved for the treatment of relapsing remitting multiple sclerosis. Analogous immunomodulatory treatment options for chronic peripheral autoimmune neuropathies are lacking.
METHODS: We tested fingolimod in the animal model of experimental autoimmune neuritis in Lewis rat. Six to eight-week-old female rats were immunized with P2 peptide and from this day on treated with fingolimod. Histology of the sciatic nerve was done to analyze T cell and macrophage cell count, intercellular adhesion molecule (ICAM) and amyloid precursor protein (APP) expression, as well as apoptotic Schwann cell counts.
RESULTS: Preventive oral treatment with 0.1 mg/kg up to 3 mg/kg fingolimod once daily dissolved in rapeseed oil completely ameliorated clinical neuritis signs. It reduced circulating peripheral blood T cells and infiltrating T cells and macrophages in the sciatic nerve, whereas at the same time, it preserved blood-nerve barrier impermeability. Most importantly, fingolimod showed beneficial properties on the pathogenic process as indicated by fewer apoptotic Schwann cells and a lower amount of amyloid precursor protein indicative of axonal damage at the peak of disease course.
CONCLUSIONS: Taken together, orally administered low-dose fingolimod showed an impressive immunomodulatory effect in the rat model of experimental autoimmune neuritis. Our current observations introduce fingolimod as an attractive treatment option for neuritis patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Neuritis treatmentISOApp (Rattus norvegicus)13782060; 13782060 RGD 
Experimental Autoimmune Neuritis treatmentIDA 13782060 RGD 

Objects Annotated

Genes (Rattus norvegicus)
App  (amyloid beta precursor protein)

Genes (Mus musculus)
App  (amyloid beta precursor protein)

Genes (Homo sapiens)
APP  (amyloid beta precursor protein)

Objects referenced in this article
Gene ATP2A1 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 Homo sapiens
Gene ATP2A2 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 Homo sapiens
Gene Atp2a1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 Mus musculus
Gene Atp2a2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 Mus musculus
Gene Atp2a1 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 Rattus norvegicus
Gene Atp2a2 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 Rattus norvegicus

Additional Information