Synthesis and Purification of MOG-IDAC: Potential Therapeutic for Multiple Sclerosis

The overall goal of this study is to evaluate the effectiveness of myelin oligodendrocyte glycoprotein-I-domain antigen conjugate (MOG-IDAC) in suppressing experimental autoimmune encephalomyelitis (EAE) in the mouse model. This mouse model is currently being used to develop therapeutic agents to treat patients with multiple sclerosis (MS). The short-term goal of this project is to produce a pure MOG-IDAC for the in vivo studies. MOG is one of the three major important proteins found in the myelin sheath. It behaves as an antigen to activate the immune cells to cause damage on the nerve cells of the central nervous system (CNS) of MS patients. Previously, the I-domain protein was conjugated to several peptides from myelin proteolipid protein (PLP) to make PLP-IDAC, which can suppress EAE in the mouse model stimulated with PLP in Complete Freund Adjuvant (CFA). In this project, we synthesized MOG-IDAC to evaluate its efficacy in MOG-stimulated EAE in the mouse model. Previously, we have successfully synthesized MOG-IDAC by reacting MOG-Cys with γ-maleimidobutyryloxy-(GMB)-I-domain to make MOG-IDAC. Unfortunately, we could not produce a sufficient quantity of MOG-IDAC for the animal study. This is due to the insoluble property of MOG-Cys. Recently, we successfully produced soluble MOG-PEG-Cys for conjugation to GMB-I-domain. We hope to produce a sufficient amount of MOG-IDAC and evaluate its efficacy in the in vivo studies.