Abstract Details

Title RNS60, a Novel Therapeutic, Suppresses Relapsing-Remitting EAE Via Tregs: Implications for MS Therapy

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 181

Objective

Background BACKGROUND: In multiple sclerosis (MS) and other autoimmune diseases, autoreactive T cells overcome the weakened suppression by a reduced number of regulatory T cells (Tregs). Upregulation or maintenance of Tregs function may therefore have therapeutic efficacy. RNS60, a CSN-containing saline devoid of an active pharmaceutical ingredient, suppresses the progression of RR-EAE. Here we report that this effect is based on induction of Tregs.

Design/Methods DESIGN/METHODS: RNS60 was generated by subjecting normal saline to Taylor-Couette-Poiseuille flow and cavitation forces under elevated oxygen pressure. RR-EAE was induced by adoptive transfer of MBP-primed T cells in SJL/J mice. Lymph node cells (LNC) isolated from MBP-immunized mice were used to test for immune modulation by RNS60 and to induce EAE.

Results RESULTS: RNS60 prevented the loss of Tregs in MBP-primed LNCs, as indicated by elevated mRNA levels of Foxp3, CD25, CD62L, and CTLA4, as well as elevated levels of intracellular Foxp3 and cell surface CD4 and CD25 as measured by FACS. This effect was abrogated by addition of an NO donor (DETA-NONOate), demonstrating that it is mediated via reduction of iNOS and nitric oxide (NO) by RNS60. In addition, RNS60-induced Tregs suppressed the expression of IFN-? by effector T cells. Remarkably, a single injection of RNS60-induced Tregs significantly ameliorated clinical symptoms of RR-EAE in female mice. A function-blocking CD25 antibody abrogated the therapeutic effects of RNS60, confirming that RNS60's protective effect is mediated by induction of Tregs.

Conclusions CONCLUSIONS: These data demonstrate that RNS60 induces functionally active Tregs via decreased iNOS expression and NO production. The ability to confer a therapeutic effect through induction of functional Tregs with a nontoxic, physically modified saline may have significant implications for the treatment of MS.

Authors/Disclosures
Susanta Mondal, PhD (Rush University) PRESENTER	No disclosure on file
Supurna Ghosh, PhD (Revalesio)	Dr. Ghosh has received personal compensation for serving as an employee of Revalesio Corporation.
Richard Watson, MD (Revalesio Corporation)	No disclosure on file
	No disclosure on file
	No disclosure on file

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