Nanoformulated Recombinant Human Myelin Basic Protein and Rituximab Modulate Neuronal Perturbations in Experimental Autoimmune Encephalomyelitis in Mice

Abstract

Introduction Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE). Methods EAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund’s adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2’, 3’ cyclic nucleotide 3’ phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses. Results The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α. Conclusion Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.

Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice

“…PLGA conjugated with MOG 35-55 was recently shown to tolerize MOG 35-55 EAE and reduce the severity of disease in a spatiotemporal fashion, requiring serial exposure to immunosuppressant/tolerizing agent rapamycin followed by the antigen [ 9 , 10 ]. A similar PLGA nanoparticles approach for EAE mice has been reported for intervention using rituximab-conjugated PLGA nanoparticles with myelin base protein (MBP), which is expressed on the surface of the myelin sheath, similar to MOG [ 11 ]. Thus, PLGA nanoparticles targeting autoantigen-reactive B cells hold promise for future clinical applications.…”