May 6, 2020

IC100: a novel anti-ASC monoclonal antibody improves functional outcomes in an animal model of multiple sclerosis

Journal of Neuroinflammation
Haritha L DesuRobert W Keane

Abstract

The inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is involved in immune signaling by bridging the interactions between inflammasome sensors and caspase-1. Strong experimental evidence has shown that ASC-/- mice are protected from disease progression in animal models of multiple sclerosis (MS), suggesting that targeting inflammasome activation via ASC inhibition may be a promising therapeutic strategy in MS. Thus, the goal of our study is to test the efficacy of IC100, a novel humanized antibody targeting ASC, in preventing and/or suppressing disease in the experimental autoimmune encephalomyelitis (EAE) model of MS. We employed the EAE model of MS where disease was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Mice were treated with vehicle or increasing doses of IC100 (10, 30, and 45 mg/kg) and clinical disease course was evaluated up to 35 days post EAE induction. Immune cell infiltration into the spinal cord and microglia responses were assessed. We show that IC100 treatment reduced the severity of EAE when compared to vehicle-treated controls. At a dose of 30 mg/kg, IC100 significantly reduced the number of CD4+ and CD8+ T ce...Continue Reading

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Mentioned in this Paper

Oligodendrocyte-Myelin Glycoprotein
Inflammatory Response
Immunization
Laboratory mice
Caspase-1
CARD14 protein, human
Objective (Goal)
NLRP3 Inflammasome Activation
CD8-Positive T-Lymphocytes
Immune Cell Activation Process

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