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International Congress on Neuroimmunology and Therapeutics

San Francisco, USA

Stephen D. Miller

Northwestern University, USA

Title: Therapeutic Infl ammatory Monocyte Modulation using MARCO-Targeting Carboxylated Immune- Modifying Nanoparticles for Amelioration of Neuroinfl ammatory Disease

Biography

Biography: Stephen D. Miller

Abstract

Inflammatory monocyte-derived effector cells are speculated to play a major pathologic role in the pathogenesis of numerous inflammatory neurological diseases. However, no treatment option currently exists that is capable of specifi cally modulating these cells. We show that intravenously infused 500 nm diameter negatively-charged, biodegradable immune-modifying-nanoparticles (IMPs) formulated from the FDA-approved biopolymer, poly(lactic-co-glycolic) acid (PLGA), are specifi cally taken up by infl ammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer traffi cked to sites of infl ammation, rather, IMP infusion caused their sequestration in the spleen (through apoptotic cell clearance mechanisms) and ultimately caspase 3-mediated apoptosis. Administration of IMPs immediately following disease initiation in mouse models of relapsing experimental autoimmune encephalomyelitis (R-EAE), acute spinal cord injury, epilepsy and lethal West Nile virus encephalitis, markedly reduced monocyte accumulation at CNS infl ammatory foci, signifi cantly reduced disease symptoms and promoted tissue repair. Together these data highlight the intricate interplay between scavenger receptors, the spleen and infl ammatory monocyte function; indicate a major pathologic role for blood-borne inflammatory monocytes rather than CNS-resident microglia in a variety of infectious and non-infectious neuroinflammatory diseases; and support the translation of IMPs for therapeutic use in a range of neuroinflammatory diseases caused or potentiated by inflammatory monocytes.

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