Abstract Details

Title Therapeutic Laquinimod Treatment Restores Axon Myelination, Callosal Conduction and Motor Deficit in a Chronic Mouse Model of Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 197

Objective

Background BACKGROUND: Laquinimod is an orally administered CNS-active immunomodulator. Phase III data in RRMS patients indicate clear effects of laquinimod 0.6mg on clinical disease activity as evidenced by slowing the progression of disability, reducing the rate of MRI-measured brain volume loss and reducing relapse rates, all coupled with a favorable safety and tolerability profile.

Design/Methods DESIGN/METHODS: 8-week-old PLP_EGFP C57BL/6 mice were treated with 5mg or 25 mg/kg/day of laquinimod. Treatment groups received daily oral gavages of laquinimod dissolved in water starting on day 15 or day 21 after first MOG immunization. EAE clinical scores and rotorod was performed throughout the disease course. Immune analysis of splenocytes, electrophysiology conduction of corpus callosum axons, and immunohistochemistry of brain and spinal cord was performed.

Results RESULTS: Therapeutic Laquinimod treatment during EAE significantly improved EAE disease scores and Rotorod motor performance. Laquinimod treatment reduced Th1 cytokines: IFN-[lambda], TNF-?, and IL-17; Th2 cytokine IL-5; and MMP9. This was supported by a significant decrease in reactive astrocytes, activated microglia and T cells in the brain. Numbers of myelinated axons and mature oligodendrocytes was increased in the spinal cord and brain of Laquinimod-treated groups. Laquinimod treatment in EAE group significantly improved callosal conduction and restored axon refractoriness closer to normal levels.

Conclusions CONCLUSIONS: Therapeutic laquinimod treatment has beneficial effects in the EAE model due to its anti-inflammatory and positive effects on oligodendrocyte numbers and myelin density. These results further support laquinimod potential role in the treatment of MS.

Authors/Disclosures
Spencer Moore PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Seema K. Tiwari-Woodruff, PhD (School of Medicine at UCR)	No disclosure on file
	No disclosure on file

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