Targeting innate receptors with MIS416: A new strategy to treat multiple sclerosis 
(Seminars)
31 July 2012
3.30pm
Venue: Room 501.505, Level 5, Building 501, Faculty of Medical and Health Sciences, Grafton Campus
Contact info: Robyn McDonald
Contact email: r.mcdonald@auckland.ac.nz
Department of Molecular Medicine and Pathology seminar by Associate Professor Anne La Flamme, School of Biological Sciences, Victoria University.
Modification of the innate immune cell environment has recently been recognized as a viable treatment strategy for reducing autoimmune disease pathology. MIS416 is a microparticle developed by Innate Immunotherapeutics that targets the innate receptors, NOD2 and TLR9. It is a promising new therapeutic for progressive multiple sclerosis and has just completed a phase 2a trial; however, the precise mechanism for disease reduction in patients is unknown. Thus, using mouse models we are investigating the pathways by which activation of TLR9 and NOD2 modify the innate immune environment and the subsequent T cell-mediated autoimmune responses. We have found that MIS416 has profound effects on the Th subset balance by depressing Th17 and Th2 development, sustaining Th1 responses, and augmenting splenic regulatory T cells. These effects coincided with increased levels of serum IFN-γ induced by MIS416 treatment. We believe that this enhanced systemic IFN-γ is key to the MIS416-mediated protection as serum levels correlate strongly with disease reduction and the protective effect of MIS416 is abrogated in IFN-γ-deficient animals. Together, these studies indicate that administration of MIS416, which initially targets innate cells, reshapes autoimmune T cell responses and in an IFN-γ-dependent manner leads to a significant reduction in CNS inflammation and disease.
