Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice
2014 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 69, 134-143 p.Article in journal (Refereed) Published
Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event and therefore a suitable therapeutic target 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. An α-synuclein protofibril-selective monoclonal antibody, mAb47, was evaluated in the (Thy-1)-h[A30P] α-synuclein transgenic mouse model, featuring an age- and motor dysfunction-associated increase of α-synuclein protofibrils in the CNS. As measured by ELISA, mAb47-treated mice displayed significantly lower levels of both soluble and membrane-associated protofibrils in the spinal cord. In addition, a trend for increased survival as a result of reduced motor symptoms was observed with antibody treatment. Taken together, this study demonstrates reduced levels of pathogenic α-synuclein and indicates a reduction of motor dysfunction in transgenic mice upon peripheral administration of an α-synuclein protofibril-selective antibody. Thus, immunotherapy with antibodies targeting toxic α-synuclein species holds promise as a future disease-modifying treatment in Parkinson’s disease and related disorders.
Place, publisher, year, edition, pages
2014. Vol. 69, 134-143 p.
Alpha-synuclein, Parkinson´s disease, Oligomers, Monoclonal antibody, Immunotherapy
Immunology in the medical area Neurosciences
Research subject Neuroscience; Geriatrics
IdentifiersURN: urn:nbn:se:uu:diva-204463DOI: 10.1016/j.nbd.2014.05.009ISI: 000339538900013PubMedID: 24851801OAI: oai:DiVA.org:uu-204463DiVA: diva2:639805
Manuscript title: Reduced pathology in (Thy-1)-h [A30P]α-synuclein transgenic mice following immunotherapy with an α-synuclein protofibril-selective antibody
Alternative title: Immunotherapy targeting alpha-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P]alpha-synuclein mice2013-08-092013-08-062014-09-07Bibliographically approved