Title : Guidance on MS animal model development: Experimental autoimmune encephalomyelitis models induced by different myelin oligodendrocyte glycoproteins exhibit differentiated pharmacological responses

Abstract:

Up-to-date, experimental autoimmune encephalomyelitis (EAE) represents the most commonly used model for studying autoimmune-mediated myelin degradation in multiple sclerosis (MS). The immunological and neurobiological mechanisms underlying the pathogenesis, progression, and prognosis of MS are complicated. Myelin oligodendrocyte glycoproteins (MOG) 35-55 and MOG1-128 are commonly used peptides for EAE model induction and the selection of MOG is often investigator’s preferences.

In this presentation, the pharmacologic responses of anti-inflammatory drugs with different mechanisms of actions (MOAs) were evaluated using EAE models induced by either myelin oligodendrocyte glycoprotein MOG35-55 or MOG1-128. The animals with EAE were treated with different anti-MS medications, including three (3) B cell-mediated agents and two (2) T cell-mediated agents, respectively. Clinical symptoms were monitored and scored, and pharmacodynamic markers including cytokine secretion, inflammatory cell infiltration, and demyelination in spinal cord were analyzed. Our results demonstrated that induction of EAE by different myelin antigens resulted in differential pharmacologic responses to drugs with specific MOAs. The MOG35-55-induced EAE model only responded to T cell-modulating drugs, whereas the MOG1-128-induced EAE model exhibited therapeutic sensitivity against both T cell- and B cell-modulating agents.

The data suggest the MOG35-55 peptide-induced EAE model is suitable for assessing T cell-modulating agents while MOG1-128-induced model can be employed to evaluate both T cell- and B cell- odulating agents. Due to complex pathogenesis of the disease and interplays between immunological and neurological responses, the finding derived from this work may shed lights on better understanding of disease biology and provide MS animal model preference.

Audience Take Away:

• On MS animal model selection and application
• Will help researchers on MS animal model selection and application
• Deeper understanding and new insights of MS animal modeling.

Biography:

Dr. Yang finished his Ph.D. on Cell Biology and completed an extensive Post-Doctoral training at University of Calgary/Tom Baker Cancer Centre, Canada. He has ~30 years of translational and innovative drug development experience on cancer and inflammation from a range of leading pharmaceutical organizations, including Celgene, Amgen, Crown Biosciences, Kosan Biosciences and ImaginAb Inc. He has led or crucially contributed to drug discovery programs involving >20 novel targets in the areas of gene therapy, epigenetics, targeted therapy and I/O, which led to 15 INDs or Phase-III development.

Dr. Yang’s expertise focuses on translational medicine and translational research in cancer and inflammation and he has published ~100 research papers or reports. Dr. Yang currently serves as an Executive Director on translational sciences, State Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Pharma Group. He held several management positions in the biotech industry including Executive Director, Cancer Biology, Global Scientific Research Innovation Organization of Crown Biosciences, Senior Director of Cancer Pharmacology, Crown Biosciences, and Head of Pharmacology at ImaginAb Inc.