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Long-term neuroprotection and neurorestoration by glial cell-derived neurotrophic factor microspheres for the treatment of Parkinson's disease§

Authors

  • Elisa Garbayo PhD,

    1. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain
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  • Eduardo Ansorena PhD,

    1. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain
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  • Jose Luis Lanciego PhD,

    1. Área de Neurociencias, CIMA, Universidad de Navarra, Pamplona, Spain
    2. Ciberned, Pamplona, Spain
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  • María Jose Blanco-Prieto PhD,

    Corresponding author
    1. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain
    • Universidad de Navarra, Avda. Pío XII 55, E-31008 Pamplona, Spain
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  • María S. Aymerich PhD

    Corresponding author
    1. Área de Neurociencias, CIMA, Universidad de Navarra, Pamplona, Spain
    2. Ciberned, Pamplona, Spain
    3. Departamento de Bioquímica y Biología Molecular, Universidad de Navarra, Pamplona, Spain
    • Universidad de Navarra, Avda. Pío XII 55, E-31008 Pamplona, Spain
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  • Funding agencies: This work was supported by the UTE-project/Foundation for Applied Medical Research (FIMA), by the Department of Health (63/04) and Education (17/04) of the Government of Navarra, the Mapfre Medicine Foundation, and Caja Navarra Foundation.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

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 μg 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. © 2011 Movement Disorder Society

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