Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease

Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents ("Seldegs," for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies of other specificities. Seldeg treatment of mice during antibody-mediated exacerbation of experimental autoimmune encephalomyelitis by patient-derived MOG-specific antibodies results in disease amelioration. Consistent with their therapeutic effects, Seldegs deliver their targeted antibodies to Kupffer and liver sinusoidal endothelial cells that are known to have tolerogenic effects. Our results show that Seldegs can ameliorate disease mediated by MOG-specific antibodies and indicate that this approach also has the potential to treat other autoimmune diseases where the specific clearance of antibodies is required. Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents ("Seldegs," for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies of other specificities. Seldeg treatment of mice during antibody-mediated exacerbation of experimental autoimmune encephalomyelitis by patient-derived MOG-specific antibodies results in disease amelioration. Consistent with their therapeutic effects, Seldegs deliver their targeted antibodies to Kupffer and liver sinusoidal endothelial cells that are known to have tolerogenic effects. Our results show that Seldegs can ameliorate disease mediated by MOG-specific antibodies and indicate that this approach also has the potential to treat other autoimmune diseases where the specific clearance of antibodies is required.