Sep 4, 2019

Myeloperoxidase Molecular MRI Reveals Synergistic Combination Therapy in Murine Experimental Autoimmune Neuroinflammation

Radiology
Anning LiJohn W Chen

Abstract

Background Despite advances in immunomodulatory agents, most current therapies for multiple sclerosis target lymphocytes or lymphocytic function. However, therapy response may be less than optimal due to demyelination and axonal damage caused by myeloid cells. Purpose To determine if myeloperoxidase (MPO) molecular MRI can evaluate whether combination therapy targeting both lymphoid and myeloid inflammation can improve autoimmune neuroinflammation compared with either drug alone, even at suboptimal doses. Materials and Methods Four groups of 94 female mice (8-10 weeks old) were induced with experimental autoimmune encephalomyelitis (EAE) from August 2, 2016, to March 30, 2018, and divided into saline control (n = 22), 4-aminobenzoic acid hydrazide (ABAH) therapy group (n = 19), glatiramer acetate (GA) therapy group (n = 22), and combination therapy group (n = 31). Mice were administered suboptimal doses of ABAH, an irreversible inhibitor of MPO; GA, a first-line multiple sclerosis drug; both ABAH and GA; or saline (control). Mice were imaged with bis-5-hydroxytryptamide-diethylenetriaminepentaacetate gadolinium (hereafter, MPO-Gd) MRI. One-way analysis of variance, two-way analysis of variance, Kurskal-Wallis, and log-rank test...Continue Reading

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Mentioned in this Paper

Glatiramer acetate
Magnetic Resonance Imaging
Combination Drug Therapy
Kruskal-Wallis Test
Lymphoid Cells
BAG3
Myeloid Cells
Axon
Pharmacologic Substance
MPO

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