Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/5783 https://doi.org/10.1016/S0168-3659(02)00353-X |
Resumo: | Glial cell line-derived neurotrophic factor (GDNF) holds great promise for the treatment of Parkinson's disease. In humans, its intracerebroventricular administration leads to limiting side effects. Direct parenchymal delivery using mechanical means, or cell and gene therapy represent potential alternatives. In the present study, a representative of each of these three approaches, i.e. polymer rods, genetically modified encapsulated cells and lentiviral vectors was analyzed for its ability to release GDNF in the striatum of rats. One week post-surgery, GDNF was detected over a distance of 4 mm with all three methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. Nanogram range of GDNF was measured with all methods at 1 week. At 4 weeks, GDNF levels decreased significantly with rods, whereas they remained stable with encapsulated cells and lentiviral vectors. We conclude that all three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application. |
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Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectorsCNS deliveryNeurotrophic factorsPolymer rodsCell encapsulationLentiviral vectorsGlial cell line-derived neurotrophic factor (GDNF) holds great promise for the treatment of Parkinson's disease. In humans, its intracerebroventricular administration leads to limiting side effects. Direct parenchymal delivery using mechanical means, or cell and gene therapy represent potential alternatives. In the present study, a representative of each of these three approaches, i.e. polymer rods, genetically modified encapsulated cells and lentiviral vectors was analyzed for its ability to release GDNF in the striatum of rats. One week post-surgery, GDNF was detected over a distance of 4 mm with all three methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. Nanogram range of GDNF was measured with all methods at 1 week. At 4 weeks, GDNF levels decreased significantly with rods, whereas they remained stable with encapsulated cells and lentiviral vectors. We conclude that all three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application.http://www.sciencedirect.com/science/article/B6T3D-47903SW-1/1/6e1fe20b6e31450aa7a03ca03fb4fc3f2003info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5783http://hdl.handle.net/10316/5783https://doi.org/10.1016/S0168-3659(02)00353-XengJournal of Controlled Release. 87:1-3 (2003) 107-115Bensadoun, Jean-CharlesPereira de Almeida, LuisFine, Eric G.Tseng, Jack L.Déglon, NicoleAebischer, Patrickinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-11-06T16:59:38Zoai:estudogeral.uc.pt:10316/5783Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:18.241260Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
title |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
spellingShingle |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors Bensadoun, Jean-Charles CNS delivery Neurotrophic factors Polymer rods Cell encapsulation Lentiviral vectors |
title_short |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
title_full |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
title_fullStr |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
title_full_unstemmed |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
title_sort |
Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors |
author |
Bensadoun, Jean-Charles |
author_facet |
Bensadoun, Jean-Charles Pereira de Almeida, Luis Fine, Eric G. Tseng, Jack L. Déglon, Nicole Aebischer, Patrick |
author_role |
author |
author2 |
Pereira de Almeida, Luis Fine, Eric G. Tseng, Jack L. Déglon, Nicole Aebischer, Patrick |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Bensadoun, Jean-Charles Pereira de Almeida, Luis Fine, Eric G. Tseng, Jack L. Déglon, Nicole Aebischer, Patrick |
dc.subject.por.fl_str_mv |
CNS delivery Neurotrophic factors Polymer rods Cell encapsulation Lentiviral vectors |
topic |
CNS delivery Neurotrophic factors Polymer rods Cell encapsulation Lentiviral vectors |
description |
Glial cell line-derived neurotrophic factor (GDNF) holds great promise for the treatment of Parkinson's disease. In humans, its intracerebroventricular administration leads to limiting side effects. Direct parenchymal delivery using mechanical means, or cell and gene therapy represent potential alternatives. In the present study, a representative of each of these three approaches, i.e. polymer rods, genetically modified encapsulated cells and lentiviral vectors was analyzed for its ability to release GDNF in the striatum of rats. One week post-surgery, GDNF was detected over a distance of 4 mm with all three methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. Nanogram range of GDNF was measured with all methods at 1 week. At 4 weeks, GDNF levels decreased significantly with rods, whereas they remained stable with encapsulated cells and lentiviral vectors. We conclude that all three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application. |
publishDate |
2003 |
dc.date.none.fl_str_mv |
2003 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/5783 http://hdl.handle.net/10316/5783 https://doi.org/10.1016/S0168-3659(02)00353-X |
url |
http://hdl.handle.net/10316/5783 https://doi.org/10.1016/S0168-3659(02)00353-X |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Controlled Release. 87:1-3 (2003) 107-115 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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