Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice

摘要: Several lines of evidence suggest that accumulation aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event Parkinson's disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against α-synuclein as a promising novel treatment strategy. Since large oligomers, or protofibrils, been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive therapeutic targets. support this, (Thy-1)-h[A30P] transgenic mice motor dysfunction symptoms were found display increased levels protofibrils CNS. An protofibril-selective monoclonal antibody (mAb47) was evaluated this mouse model. As measured by ELISA, 14month old treated for 14weeks weekly intraperitoneal injections mAb47 displayed significantly lower both soluble membrane-associated spinal cord. Besides demonstrated, reduction upon peripheral administration indicated. Thus, targeting toxic holds promise future disease-modifying related