Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease

Shilpa Ramaswamy, Jodi McBride, Christopher D. Herzog, Eugene Brandon, Mehdi Gasmi, Raymond T. Bartus, Jeffrey H. Kordower

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)375-384
Number of pages10
JournalNeurobiology of Disease
Volume26
Issue number2
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

Neurturin
Corpus Striatum
Huntington Disease
Genetic Therapy
Neurons
Rotarod Performance Test
Neurodegenerative Diseases
Cerebral Cortex
3-nitropropionic acid

Keywords

  • 3-Nitropropionic acid
  • Adenoassociated viral vector
  • Gene therapy
  • Huntington's disease
  • Neurturin

ASJC Scopus subject areas

  • Neurology

Cite this

Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease. / Ramaswamy, Shilpa; McBride, Jodi; Herzog, Christopher D.; Brandon, Eugene; Gasmi, Mehdi; Bartus, Raymond T.; Kordower, Jeffrey H.

In: Neurobiology of Disease, Vol. 26, No. 2, 05.2007, p. 375-384.

Research output: Contribution to journalArticle

Ramaswamy, Shilpa ; McBride, Jodi ; Herzog, Christopher D. ; Brandon, Eugene ; Gasmi, Mehdi ; Bartus, Raymond T. ; Kordower, Jeffrey H. / Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease. In: Neurobiology of Disease. 2007 ; Vol. 26, No. 2. pp. 375-384.
@article{2a07e9ab148f4d8c933216d0fd6c2981,
title = "Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease",
abstract = "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.",
keywords = "3-Nitropropionic acid, Adenoassociated viral vector, Gene therapy, Huntington's disease, Neurturin",
author = "Shilpa Ramaswamy and Jodi McBride and Herzog, {Christopher D.} and Eugene Brandon and Mehdi Gasmi and Bartus, {Raymond T.} and Kordower, {Jeffrey H.}",
year = "2007",
month = "5",
doi = "10.1016/j.nbd.2007.01.003",
language = "English (US)",
volume = "26",
pages = "375--384",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease

AU - Ramaswamy, Shilpa

AU - McBride, Jodi

AU - Herzog, Christopher D.

AU - Brandon, Eugene

AU - Gasmi, Mehdi

AU - Bartus, Raymond T.

AU - Kordower, Jeffrey H.

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

KW - 3-Nitropropionic acid

KW - Adenoassociated viral vector

KW - Gene therapy

KW - Huntington's disease

KW - Neurturin

UR - http://www.scopus.com/inward/record.url?scp=34147166160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147166160&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2007.01.003

DO - 10.1016/j.nbd.2007.01.003

M3 - Article

C2 - 17336076

AN - SCOPUS:34147166160

VL - 26

SP - 375

EP - 384

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 2

ER -