Effective GDNF brain delivery using microspheres-A promising strategy for Parkinson’s disease

Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres...

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Detalles Bibliográficos
Autores: Garbayo, E. (Elisa)|||/items/c0fa35e4-82c5-44f7-b300-740027106dba, Monter-Menei, C.N. (C.N.)|||/items/5fb793e9-9d56-4a84-a574-fa056887d2fd, Ansorena-Artieda, E. (Eduardo)|||/items/eee6c2d6-f73a-48d3-a5f8-fe090b677c82, Lanciego-Pérez, J.L. (José Luis)|||/items/d2d4dbfe-4daf-4103-89ec-2ebf41b65cd1, Aymerich-Soler, M.S. (María Soledad)|||/items/f65ae32b-d1a8-4fa4-ba9f-b8b10241f470, Blanco-Prieto, M.J. (María José)|||/items/93e177db-635f-456f-b672-b79ef8befc40
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/19580
Acceso en línea:https://hdl.handle.net/10171/19580
Access Level:acceso abierto
Palabra clave:GDNF
PLGA microparticles
TROMS
Serum IgG antibodies against GDNF
Parkinson´s disease
Descripción
Sumario:Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamine-induced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use.

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