Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease
Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neu...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-05-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996107000216 |
| _version_ | 1831583051177525248 |
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| author | Shilpa Ramaswamy Jodi L. McBride Christopher D. Herzog Eugene Brandon Mehdi Gasmi Raymond T. Bartus Jeffrey H. Kordower |
| author_facet | Shilpa Ramaswamy Jodi L. McBride Christopher D. Herzog Eugene Brandon Mehdi Gasmi Raymond T. Bartus Jeffrey H. Kordower |
| author_sort | Shilpa Ramaswamy |
| collection | DOAJ |
| description | Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neuroprotection in the rat 3-nitropropionic acid (3NP) model of HD. Rats received AAV2-NTN (CERE-120), AAV2-eGFP or Vehicle, followed 4 weeks later by the mitochondrial toxin 3NP. 3NP induced motor impairments were observed on the rotarod test, the platform test, and a clinical rating scale in all groups. However, each of these deficits was attenuated by AAV2-NTN (CERE-120). Stereological counts revealed a significant protection of NeuN-ir striatal neurons from 3NP toxicity by AAV2-NTN. These data support the concept that AAV2-NTN might be a valuable treatment for patients with Huntington's disease. |
| first_indexed | 2024-12-17T20:35:24Z |
| format | Article |
| id | doaj.art-045d571a862e4c1d8a56b3ff08eedf21 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:35:24Z |
| publishDate | 2007-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-045d571a862e4c1d8a56b3ff08eedf212022-12-21T21:33:28ZengElsevierNeurobiology of Disease1095-953X2007-05-01262375384Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's diseaseShilpa Ramaswamy0Jodi L. McBride1Christopher D. Herzog2Eugene Brandon3Mehdi Gasmi4Raymond T. Bartus5Jeffrey H. Kordower6Department of Neuroscience, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USADepartment of Neuroscience, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USACEREgene Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USACEREgene Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USACEREgene Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USACEREgene Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USADepartment of Neuroscience, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USA; Corresponding author. Fax: +1 312 563 3571.Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neuroprotection in the rat 3-nitropropionic acid (3NP) model of HD. Rats received AAV2-NTN (CERE-120), AAV2-eGFP or Vehicle, followed 4 weeks later by the mitochondrial toxin 3NP. 3NP induced motor impairments were observed on the rotarod test, the platform test, and a clinical rating scale in all groups. However, each of these deficits was attenuated by AAV2-NTN (CERE-120). Stereological counts revealed a significant protection of NeuN-ir striatal neurons from 3NP toxicity by AAV2-NTN. These data support the concept that AAV2-NTN might be a valuable treatment for patients with Huntington's disease.http://www.sciencedirect.com/science/article/pii/S0969996107000216Huntington’s diseaseNeurturinGene therapy3-Nitropropionic acidAdenoassociated viral vector |
| spellingShingle | Shilpa Ramaswamy Jodi L. McBride Christopher D. Herzog Eugene Brandon Mehdi Gasmi Raymond T. Bartus Jeffrey H. Kordower Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease Neurobiology of Disease Huntington’s disease Neurturin Gene therapy 3-Nitropropionic acid Adenoassociated viral vector |
| title | Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease |
| title_full | Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease |
| title_fullStr | Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease |
| title_full_unstemmed | Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease |
| title_short | Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease |
| title_sort | neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3 nitropropionic acid rat model of huntington s disease |
| topic | Huntington’s disease Neurturin Gene therapy 3-Nitropropionic acid Adenoassociated viral vector |
| url | http://www.sciencedirect.com/science/article/pii/S0969996107000216 |
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