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Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Lannfelt)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Lannfelt)
BioArctic Neuroscience AB.
BioArctic Neuroscience AB.
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2014 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 69, 134-143 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Alpha-synuclein, Parkinson´s disease, Oligomers, Monoclonal antibody, Immunotherapy
National Category
Immunology in the medical area Neurosciences
Research subject
Neuroscience; Geriatrics
URN: 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 mice

Available from: 2013-08-09 Created: 2013-08-06 Last updated: 2014-09-07Bibliographically approved

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Lindström, VeronicaFagerqvist, ThereseBergström, JoakimLannfelt, LarsIngelsson, Martin
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