Abstract Details

Title Laquinimod Treatment Reverses Cortical and Hippocampus Pathology Due to Inflammatory Demyelination in a Chronic Mouse Model of Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P06 - (-)

Poster/Presentation
Number 126

Objective

Background BACKGROUND: Laquinimod is an oral, once-daily CNS-active immunomodulator for the treatment of MS. 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 brain atrophy and relapse rates.

Design/Methods DESIGN/METHODS: 8-week-old C57BL/6 mice were pre- and post-treated by daily oral gavages with 25 mg/kg/day of Laquinimod starting on day 0 or day 21 after first MOG immunization. EAE clinical scores were assessed throughout the disease course. Golgi staining, immunohistochemistry of the brain and electron microscopy was performed 36-40 days post-disease induction. Inflammation, demyelination, specific neuronal dendrites, apoptosis, and pre- and post- synaptic puncta quantification were analyzed from brain sections corresponding to plates 42-47 from the atlas of Franklin and Paxinos.

Results RESULTS: Mean clinical disease scores of EAE mice with Laquinimod treatment were significantly improved throughout disease. Laquinimod treatment reduced the number of lesions and overall demyelination, neurodegeneration and microglia activation in the cortical layers and hippocampus. Callosal projection neurons from cortical layer II/III and V, as well as neurons from hippocampus CA1 were examined . Laquinimod treatment increased number of synaptic puncta and improved neuronal dendrite integrity . Laquinimod treatment during EAE significantly decreased number of apoptotic cells in the cortical layers and the hippocampus.

Conclusions CONCLUSIONS: Our results show and support a role of Laquinimod in the treatment of EAE- and potentially MS-related cortical and hippocampus pathology.

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

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