Laquinimod Add on Effect on Glatiramer Acetate as Well as INFb Treatments (P04.142)

Abstract

Objective: Studying whether laquinimod treatment added on top of either GA (glatiramer acetate) or IFNb would result in an additive effect on disease severity in MOG-induced EAE. Background Laquinimod is an orally administered CNS-active immunomodulator. Phase III data in RRMS patients indicate clear effects of laquinimod 0.6mg on disease progression and on the accumulation of brain-tissue loss, as measured by MRI, coupled with a favorable safety and tolerability profile. Laquinimod has shown a significant effect in Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. In the EAE model, laquinimod has been shown to significantly abrogate disease severity. It was suggested that Laquinimod exhibits its effect via NFkB signaling inhibition. It was shown to affect CNS residential cells as astrocytes and microglia resulting in reduction of proinflammatory cytokines. Glatiramer acetate (GA), a well-known disease modifying treatment for relapsing RRMS, is an immunomodulator that significantly inhibits disease activity in EAE. GA was shown to bind to various class II major histocompatibility complex (MHC) molecules and to create GA specific Th2 cells. These cells are migrating into the CNS and secreting anti inflammatory cytokines. INFb-which is also in use for RRMS treatment is effective in reducing inflammatory activity in EAE. Laquinimod has shown efficacy, using IFNb knock out mouse model, suggesting that laquinimod efficacy is IFNb independent. Design/Methods: MOG induced EAE C57BL/6 mice were treated with Laquinimod (5 and 25mg/kg) alone or together with suboptimal dose of GA (12.5mg/kg) or IFNb (500,000 and 50,000 IU/mouse). All treatments were started 1 day after immunization. Scoring of EAE clinical signs were carried out daily. Results: Both GA/laquinimod and IFNb/laquinimod adjunct treatment resulted in improved efficacy when compared to each treatment alone. Conclusions: These results suggesting the use of both treatment regimens together as a potential treatment for RRMS patients. Supported by: Teva Pharmaceutical industries. Disclosure: Dr. Hayardeny Nisimov has nothing to disclose. Dr. Birnberg has nothing to disclose. Dr. Raymond has received research support from TEVA Pharmaceutical. Dr. Fine has received research support from Teva Pharmaceutical. Dr. Kaye has received personal compensation for activities with Teva Neuroscience as an employee. Dr. Kaye has received research support from Teva Neuroscience.