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

Autor: Desu HL; University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Plastini M; University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Illiano P; University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Bramlett HM; University of Miami Miller School of Medicine, Miami, FL, 33136, USA.; InflamaCORE, LLC, Miami, FL, 33156, USA.; Bruce W. Carter, Department of Veterans Affairs Medical Center, Miami, FL, 33136, USA., Dietrich WD; University of Miami Miller School of Medicine, Miami, FL, 33136, USA.; InflamaCORE, LLC, Miami, FL, 33156, USA., de Rivero Vaccari JP; University of Miami Miller School of Medicine, Miami, FL, 33136, USA.; InflamaCORE, LLC, Miami, FL, 33156, USA., Brambilla R; University of Miami Miller School of Medicine, Miami, FL, 33136, USA. r.brambilla@miami.edu.; Deparment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. r.brambilla@miami.edu.; BRIDGE Brain Research Inter Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. r.brambilla@miami.edu., Keane RW; University of Miami Miller School of Medicine, Miami, FL, 33136, USA. rkeane@miami.edu.; InflamaCORE, LLC, Miami, FL, 33156, USA. rkeane@miami.edu.; Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. rkeane@miami.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2020 May 04; Vol. 17 (1), pp. 143. Date of Electronic Publication: 2020 May 04.
DOI: 10.1186/s12974-020-01826-0
Abstrakt: Background: 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.
Methods: We employed the EAE model of MS where disease was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 35-55 ). 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.
Results: 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 cells and CD11b + MHCII + activated myeloid cells entering the spinal cord from the periphery, and reduced the number of total and activated microglia.
Conclusions: These data indicate that IC100 suppresses the immune-inflammatory response that drives EAE development and progression, thereby identifying ASC as a promising target for the treatment of MS as well as other neurological diseases with a neuroinflammatory component.
Databáze: MEDLINE
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