Laquinimod Treatment Reduces an Immunogenic Dendritic Cell Population and Protects from Autoimmune CNS Inflammation (P02.117)

Abstract

Objective: In this study we aimed to investigate whether, and how, laquinimod can prevent the occurrence of relapses in a relapsing-remitting model of MS. Background Laquinimod is an orally administered CNS-active immunomodulator. Phase III data in RRMS patients showed beneficial 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: We used C5BL/6 as well as SJL/J mice to induce EAE with the MOG peptide p35-55 or the PLP peptide p39-151, respectively. Dendritic cells (DCs) were analyzed from either spleen or lymph nodes. T cells were analyzed from spleen, lymph nodes or from the CNS. Results: C57BL/6 mice treated with laquinimod by daily oral gavage, were completely resistant to disease induction. To test whether the disease could also be modulated at a later stage, we induced disease in SJL/J mice, in a protocol that leads to a relapsing-remitting disease. We found that the mice treated with laquinimod were prevented from developing further relapse, in contrast to mice treated with vehicle only. Interestingly, we found that CD4+CD11c+ were almost completely absent in the Laquinimod treated mice, C57BL/6 as well as of the SJL/J mice. In addition, we detected an elevation in the total number of FoxP3+CD4+ regulatory T cells in the laquinimod treated animals. CD11c+CD4+ cells were previously implicated as immunogenic DCs, in contrast to CD11c+CD8+ cells shown to have immunomodulatory properties. Conclusions: We report that treatment of mice with laquinimod has distinct implications for cytokine production and T cell response. We suggest therefore that laquinimod appears to exert its disease-suppressive activity by modulating DC and T cell responses. Supported by: An unrestricted grant from Teva Pharmaceutical Industries (Netanya, Israel). Disclosure: Dr. Waisman has received personal compensation for activities with Teva Neuroscience as a consultant. Dr. Waisman has received research support from Teva Neuroscience. Dr. Masri has nothing to disclose. Dr. Jolivel has nothing to disclose. Dr. Lussi has nothing to disclose. Dr. Siffrin has nothing to disclose. Dr. Zipp has nothing to disclose.