Journal
MOVEMENT DISORDERS
Volume 26, Issue 10, Pages 1943-1947Publisher
WILEY
DOI: 10.1002/mds.23793
Keywords
Parkinson's disease; glial cell-derived neurotrophic factor; microspheres; neurodegeneration; 6-hydroxydopamine; tyrosine hydroxylase
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Funding
- UTE/Foundation for Applied Medical Research (FIMA)
- Department of Health and Education of the Government of Navarra [63/04, 17/04]
- Mapfre Medicine Foundation
- Gala Navarra Foundation
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Background: Glial cell-derived neurotrophic factor is a survival factor for dopaminergic neurons and a promising candidate for the treatment of Parkinson's disease. However, the delivery issue of the protein to the brain still remains unsolved. Our aim was to investigate the effect of long-term delivery of encapsulated glial cell-derived neurotrophic factor within microspheres. Methods: A single dose of microspheres containing 2.5 mu g of glial cell-derived neurotrophic factor was implanted intrastriatally in animals 2 weeks after a 6-hydroxydopamine lesion. Results: The amphetamine test showed a complete behavioral recovery after 16 weeks of treatment, which was maintained until the end of the study (week 30). This effect was accompanied by an increase in dopaminergic striatal terminals and neuroprotection of dopaminergic neurons. Conclusions: The main achievement was the long-term neurorestoration in parkinsonian animals induced by encapsulated glial cell-derived neurotrophic factor, suggesting that microspheres may be considered as a means to deliver glial cell-derived neurotrophic factor for Parkinson's disease treatment. (C)2011 Movement Disorder Society
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