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Bäck S, Peränen J, Galli E, et al. Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease. Brain Behav. 2013;3(2):75-88doi: 10.1002/brb3.117.
Bäck, S., Peränen, J., Galli, E., Pulkkila, P., Lonka-Nevalaita, L., Tamminen, T., Voutilainen, M. H., Raasmaja, A., Saarma, M., Männistö, P. T., & Tuominen, R. K. (2013). Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease. Brain and behavior, 3(2), 75-88. https://doi.org/10.1002/brb3.117
Bäck, Susanne, et al. "Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease." Brain and behavior vol. 3,2 (2013): 75-88. doi: https://doi.org/10.1002/brb3.117
Bäck S, Peränen J, Galli E, Pulkkila P, Lonka-Nevalaita L, Tamminen T, Voutilainen MH, Raasmaja A, Saarma M, Männistö PT, Tuominen RK. Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease. Brain Behav. 2013 Mar;3(2):75-88. doi: 10.1002/brb3.117. Epub 2013 Jan 14. PMID: 23532969; PMCID: PMC3607149.
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Brain Behav. 2013 Mar;3(2):75-88. doi: 10.1002/brb3.117. Epub 2013 Jan 14.

Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease.

Brain and behavior

Susanne Bäck, Johan Peränen, Emilia Galli, Päivi Pulkkila, Liina Lonka-Nevalaita, Tuulia Tamminen, Merja H Voutilainen, Atso Raasmaja, Mart Saarma, Pekka T Männistö, Raimo K Tuominen

Affiliations

  1. Division of Pharmacology and Toxicology Faculty of Pharmacy, University of Helsinki Helsinki, Finland.

PMID: 23532969 PMCID: PMC3607149 DOI: 10.1002/brb3.117

Abstract

Cerebral dopamine neurotrophic factor (CDNF) protein has been shown to protect the nigrostriatal dopaminergic pathway when given as intrastriatal infusions in rat and mouse models of Parkinson's disease (PD). In this study, we assessed the neuroprotective effect of CDNF delivered with a recombinant adeno-associated viral (AAV) serotype 2 vector in a rat 6-hydroxydopamine (6-OHDA) model of PD. AAV2 vectors encoding CDNF, glial cell line-derived neurotrophic factor (GDNF), or green fluorescent protein were injected into the rat striatum. Protein expression analysis showed that our AAV2 vector efficiently delivered the neurotrophic factor genes into the brain and gave rise to a long-lasting expression of the proteins. Two weeks after AAV2 vector injection, 6-OHDA was injected into the rat striatum, creating a progressive degeneration of the nigrostriatal dopaminergic system. Treatment with AAV2-CDNF resulted in a marked decrease in amphetamine-induced ipsilateral rotations while it provided only partial protection of tyrosine hydroxylase (TH)-immunoreactive cells in the rat substantia nigra pars compacta and TH-reactive fibers in the striatum. Results from this study provide additional evidence that CDNF can be considered a potential treatment of Parkinson's disease.

Keywords: 6-OHDA; AAV; CDNF; GDNF; gene therapy

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