Abstract Details

Title Immunomodulatory Effects of Bortezomib in Experimental Autoimmune Neuritis in Lewis rats

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-090

Objective We used the experimental autoimmune neuritis (EAN) in the Lewis rat to study effects of Bortezomib (BTZ).

Background BTZ was able to stop disease progression in patients with treatment refractory chronic inflammatory demyelinating polyradiculopathy (CIDP) when administered subcutaneously 1.3 mg/m² KOF at day 1, 4, 7 and 10 (Pitarokoili et al. 2017). The exact mechanisms of action remain unknown while the dose-limiting side-effect of Bortezomib is an axonal polyneuropathy.

Design/Methods To determine the minimum concentration inducing polyneuropathy we treated female Lewis rats with BTZ (0.05, 0.2 mg/kg) intraperitoneally (i.p.) and the control group with 5% DMSO. Subsequently, EAN was induced in 6 weeks old rats by P2-peptide (n=12/group). One group was treated with 0.05mg/kg BTZ i.p., control group received 5% DMSO at day 9, 13, 17 and 21. Von Frey hair-(vFH) and hot plate test were performed at day 10, 14, 18 and 22. Clinical score and weight were assessed daily. Electrophysiological analyses of sciatic nerve were performed at day 0 and 23. At day 23, we performed flow cytometric analyses of the immune cells in spleen, lymph nodes and bone marrow . Subsequently, sciatic nerve and dorsal root ganglia were analysed by immunohistology and qRT-PCR.

Results Treatment with 0.05 mg/kg BTZ i.p. improved EAN significantly, reduced inflammatory infiltrates and demyelination in the sciatic nerves and ameliorated electrophysiological neuritis signs without inducing axonal neuropathy. Furthermore, BTZ improved vFH and hot plate test. Flow cytometric analyses showed a reduction of CD4⁺, CD11b⁺ cell populations in peripheral lymph nodes.

Conclusions We revealed firstly the immunomodulatory effects of bortezomib in EAN. 0.05 mg/kg i.p. administered BTZ improves clinical EAN score, electrophysiological signs of large myelinated axons and small fiber function in vFH test, without causing neuropathy as a side-effect. The proposed relevant immunological mechanism is the modification of dendritic and B-cell populations in lymph nodes.

Authors/Disclosures
Rafael M. Klimas (St. Josef Hospital - Ruhr-University Bochum) PRESENTER	Mr. Klimas has nothing to disclose.
Melissa Sgodzai	Melissa Sgodzai has nothing to disclose.
	No disclosure on file
	No disclosure on file
Min-Suk Yoon, MD	No disclosure on file
Ralf Gold, MD (Neurologische Universitaetsklinik)	Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
Kalliopi Pitarokoili, MD (St Josefs Hospital)	Dr. Pitarokoili has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring.

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