Source:http://linkedlifedata.com/resource/pubmed/id/12075987
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2002-6-21
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| pubmed:abstractText |
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopamine neurons that has been proposed for use in the treatment of Parkinson's disease (PD). Previous studies using viral vectors to deliver GDNF in rodent models of PD have entailed administering the virus either prior to or immediately after neurotoxin-induced lesions, when the nigrostriatal pathway is largely intact, a paradigm that does not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, recombinant adeno-associated virus carrying the gene encoding GDNF (rAAV-GDNF) was administered to animals bearing a maximal lesion in the nigrostriatal system, more closely resembling fully developed PD. Rats were treated with 6-hydroxydopamine into the medial forebrain bundle and assessed by apomorphine-induced rotational behavior for 5 weeks prior to virus administration. Within 4 weeks of a single intrastriatal injection of rAAV-GDNF, unilaterally lesioned animals exhibited significant behavioral recovery, which correlated with increased expression of dopaminergic markers in the substantia nigra, the medial forebrain bundle, and the striatum. Our findings demonstrate that rAAV-GDNF is capable of rescuing adult dopaminergic neurons from near complete phenotypic loss following a neurotoxic lesion, effectively restoring a functional dopaminergic pathway and diminishing motoric deficits. These data provide further support for the therapeutic potential of rAAV-GDNF-based gene therapy in the treatment of PD.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apomorphine,
http://linkedlifedata.com/resource/pubmed/chemical/GDNF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0963-6897
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
11
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
215-27
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12075987-Animals,
pubmed-meshheading:12075987-Apomorphine,
pubmed-meshheading:12075987-Behavior, Animal,
pubmed-meshheading:12075987-Cell Line,
pubmed-meshheading:12075987-Corpus Striatum,
pubmed-meshheading:12075987-Dependovirus,
pubmed-meshheading:12075987-Disease Models, Animal,
pubmed-meshheading:12075987-Dopamine,
pubmed-meshheading:12075987-Gene Therapy,
pubmed-meshheading:12075987-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:12075987-Humans,
pubmed-meshheading:12075987-Male,
pubmed-meshheading:12075987-Medial Forebrain Bundle,
pubmed-meshheading:12075987-Motor Activity,
pubmed-meshheading:12075987-Nerve Growth Factors,
pubmed-meshheading:12075987-Oxidopamine,
pubmed-meshheading:12075987-Parkinsonian Disorders,
pubmed-meshheading:12075987-Phenotype,
pubmed-meshheading:12075987-Rats,
pubmed-meshheading:12075987-Rats, Inbred F344,
pubmed-meshheading:12075987-Substantia Nigra,
pubmed-meshheading:12075987-Tyrosine 3-Monooxygenase
|
| pubmed:year |
2002
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| pubmed:articleTitle |
Adeno-associated viral delivery of GDNF promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion.
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| pubmed:affiliation |
Alkermes, Inc., Cambridge, MA, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|