CLINICAL TRIAL SERVICES
The Buffalo Neuroimaging Analysis Center (BNAC) is a dedicated research center that has expertise in preclinical relapsing models of multiple sclerosis (MS).
The experimental autoimmune encephalomyelitis (EAE) mouse model of MS has been used widely for studying auto-immune mediated myelin degradation. Recent studies investigated immune cell activity at the meninges and its role in gray matter (GM) pathology. These studies suggest that EAE brain white matter (WM) and GM pathology mirrors cellular changes noted in post-mortem MS brain tissue and is strongly correlated with behavioral measures. Similar correlations between GM pathology and clinical outcomes were recorded in MS patients as well. These studies support the use of the EAE mouse model for studying MS therapies and WM/GM pathology.
In EAE induced by recombinant MOG, B-cell depletion prevents or leads to reversal of the established recombinant MOG-induced EAE, resulting in less central nervous system inflammation, elimination of meningeal B cells, and reduction of MOG-specific Th1 and Th17 cells. In MOG35–55 peptide-induced EAE, B cells do not become activated or efficiently polarize proinflammatory MOG-specific T cells, resulting in exacerbation of EAE with anti-CD20 treatment, and it does not impede development of Th1 or Th17 cells. Unlike immunization with the short MOG35–55 peptide, human (hu)-MOG1–125 induced EAE involves B-cell recognition of the native MOG protein; the resultant autoimmune disease is chronic with clear evidence of an ongoing immune response and active WM and GM matter infiltration by T cells, as well as formation of B-cell clusters in the meninges.
BNAC has recently established a framework for better understanding of WM and GM pathology, by conducting preclinical trials with currently FDA approved DMTs, as well as those in various stages of preclinical and clinical development, using various EAE models of MS. In particular, BNAC applied an experimental paradigm for investigating the role of B-cell depletion with the anti-CD20 antibody in the huMOG-EAE mice model. This disease model also allowed us to characterize the linking of neuroimaging outcomes with biomarker levels under conditions of efficacious B-cell depletion. We also investigated the pathology at the cellular level and the density of proliferating and non-proliferating microglial or oligodendroglial cells. BNAC longitudinally traced the GM pathological changes using various brain and spinal cord imaging measures as a proxy of disease severity, and then characterized their association with huMOG-EAE disease-induced clinical disability, immunology and histological outcomes.
FEATURED MOG-EAE CLINICAL STUDIES IN MS
- Pol S, Liang S, Schweser F, Dhanraj R, Schubart A, Preda M, Sveinsson M, Ramasamy DP, Dwyer MG, Weckbecker G, Zivadinov R (2021) Subcutaneous anti-CD20 antibody treatment delays gray matter atrophy in human myelin oligodendrocyte glycoprotein-induced EAE mice. Exp Neurol 335:113488 [Open article]
- Pol S, Schweser F, Bertolino N, Preda M, Sveinsson M, Sudyn M, Babek N, Zivadinov R (2019) Characterization of leptomeningeal inflammation in rodent experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Exp Neurol 314:82-90 [Open article]
- Valerio M, Liu HB, Heffner R, Zivadinov R, Ramanathan M, Weinstock-Guttman B, Awad AB (2011) Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis. Inflamm Res 60:457-465 [Open article]
CONTACT OUR TEAM TODAY
Part of BNAC’s mission is to help share our tools and experience with our colleagues and other industry partners. If you need help with managing a preclinical trial using MOG-EAE model, please reach out to discuss how we can assist. Our group brings decades of experience and expertise to every collaborative study and service partnership.