Siponimod ameliorates experimental autoimmune neuritis.

Area of Science:

• Neuroimmunology
• Peripheral Neuropathy Research

Background:

• Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are autoimmune peripheral neuropathies.
• Cellular immunity, alongside humoral immunity, is implicated in GBS and CIDP pathogenesis.
• Sphingosine-1-phosphate receptor 1 (S1PR1) is crucial for lymphocyte trafficking, but S1PR agonist effects on GBS/CIDP are largely unknown.

Purpose of the Study:

• To investigate the therapeutic potential of siponimod, an S1PR1 and S1PR5 agonist, in experimental autoimmune neuritis (EAN).
• EAN serves as an animal model for human autoimmune peripheral neuropathies like GBS and CIDP.

Main Methods:

• Lewis rats were immunized to induce EAN.
• Siponimod or vehicle was administered daily from day 5 to 27 post-immunization.
• Symptom severity, cytokine/transcription factor expression in lymph nodes and cauda equina (CE), and CE histology were assessed.

Main Results:

• Siponimod treatment significantly reduced symptom severity in EAN rats.
• Interferon-gamma and IL-10 mRNA expression decreased in lymph nodes and CE following siponimod administration.
• Histological analysis revealed reduced demyelination and inflammatory cell infiltration in the CE of siponimod-treated rats.

Conclusions:

• Siponimod demonstrates potential therapeutic benefits for EAN, suggesting a role in treating GBS and CIDP.
• Sonic hedgehog (Shh) and Glial cell line-derived neurotrophic factor (Gdnf), along with c-Jun, are significant factors in nerve injury recovery.