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Neurobiol Dis. 2014 Sep;69:134-43. doi: 10.1016/j.nbd.2014.05.009. Epub 2014 May 20.

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

Author information

  • 1Department of Public Health/Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • 2BioArctic Neuroscience AB, Stockholm, Sweden.
  • 3Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany.
  • 4Department of Public Health/Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Electronic address:


Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-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 α-synuclein as a promising novel treatment strategy. Since large α-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] α-synuclein transgenic mice with motor dysfunction symptoms were found to display increased levels of α-synuclein protofibrils in the CNS. An α-synuclein protofibril-selective monoclonal antibody (mAb47) was evaluated in this α-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 α-synuclein demonstrated, a reduction of motor dysfunction in transgenic mice upon peripheral administration of mAb47 was indicated. Thus, immunotherapy with antibodies targeting toxic α-synuclein species holds promise as a future disease-modifying treatment in Parkinson's disease and related disorders.

Copyright © 2014 Elsevier Inc. All rights reserved.


Immunization; Protofibril-selective antibody; α-Synuclein transgenic mice

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