| First Author | Lindström V | Year | 2014 |
| Journal | Neurobiol Dis | Volume | 69 |
| Pages | 134-43 | PubMed ID | 24851801 |
| Mgi Jnum | J:214308 | Mgi Id | MGI:5588750 |
| Doi | 10.1016/j.nbd.2014.05.009 | Citation | Lindstrom V, et al. (2014) Immunotherapy targeting alpha-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] alpha-synuclein mice. Neurobiol Dis 69:134-43 |
| abstractText | Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (alpha-synuclein) in the central nervous system (CNS) is an early pathogenic event in Parkinson's disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against alpha-synuclein as a promising novel treatment strategy. Since large alpha-synuclein oligomers, or protofibrils, have been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive as therapeutic targets. In support of this, (Thy-1)-h[A30P] alpha-synuclein transgenic mice with motor dysfunction symptoms were found to display increased levels of alpha-synuclein protofibrils in the CNS. An alpha-synuclein protofibril-selective monoclonal antibody (mAb47) was evaluated in this alpha-synuclein transgenic mouse model. As measured by ELISA, 14month old mice treated for 14weeks with weekly intraperitoneal injections of mAb47 displayed significantly lower levels of both soluble and membrane-associated protofibrils in the spinal cord. Besides the lower levels of pathogenic alpha-synuclein demonstrated, a reduction of motor dysfunction in transgenic mice upon peripheral administration of mAb47 was indicated. Thus, immunotherapy with antibodies targeting toxic alpha-synuclein species holds promise as a future disease-modifying treatment in Parkinson's disease and related disorders. |
