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Restorative Effects of Platelet Derived Growth Factor-BB in Rodent Models of Parkinson's Disease

Article type: Research Article

Authors: Zachrisson, Olof | Zhao, Ming | Andersson, Annica | Dannaeus, Karin | Häggblad, Johan | Isacson, Ruben | Nielsen, Elisabet | Patrone, Cesare | Rönnholm, Harriet | Wikstrom, Lilian | Delfani, Kristofer | McCormack, Alison L. | Palmer, Theo | Di Monte, Donato A. | Hill, Michael P. | Janson Lang, Ann Marie | Haegerstrand, Anders

Affiliations: NeuroNova AB, Fiskartorpsvägen 15, Stockholm, Sweden | Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden | The Parkinson's Institute, Sunnyvale, CA, USA | Motac Neuroscience Ltd, Manchester Science Park, Manchester, UK

Note: [] Present address: Karolinska Institute, Department of Clin Sci and Edu., Unit for Diabetes Research, Södersjukhuset, SE-11833 Stockholm, Sweden

Note: [] Correspondence to: Anders Haegerstrand, NeuroNova AB, Fiskartorpsvägen 15, SE-11433 Stockholm, Sweden. E-mail: [email protected]; Ann Marie Janson Lang, Department of Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden. E-mail: [email protected]

Note: [] Correspondence to: Anders Haegerstrand, NeuroNova AB, Fiskartorpsvägen 15, SE-11433 Stockholm, Sweden. E-mail: [email protected]; Ann Marie Janson Lang, Department of Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden. E-mail: [email protected]

Keywords: Platelet derived growth factor, Parkinson's disease, subventricular zone, progenitor cell, 6-hydroxydopamine, MPTP

DOI: 10.3233/JPD-2011-0003

Journal: Journal of Parkinson's Disease, vol. 1, no. 1, pp. 49-63, 2011

Published: 2011
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Abstract

Parkinson's disease is characterized by motor deficits caused by loss of midbrain dopaminergic neurons. Neurotrophic factors and cell transplantation have partially restored function in models of Parkinson's disease, but have had limited effects in humans. Here we show that intracerebroventricular administration of platelet-derived growth factor-BB can offer an alternative strategy to restore function in Parkinson's disease; In animal models of nigrostriatal injury, a two weeks treatment with platelet-derived growth factor-BB resulted in long-lasting restoration of striatal dopamine transporter binding sites and expression of nigral tyrosine hydroxylase. It also normalized amphetamine-induced rotational behavior in 6-hydroxydopamine lesioned rats. Platelet-derived growth factor-BB promoted proliferation of neural progenitor cells in the subventricular zone. The effects on dopaminergic neurons and functional recovery could be blocked by co-infusion with a proliferation inhibitor, indicating a link between the proliferative and anti-parkinsonian effects. Based on the current data, we consider platelet-derived growth factor-BB a clinical candidate drug for treatment of Parkinson's disease.

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