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 L.
AU - Herzog, Christopher D.
AU - Brandon, Eugene
AU - Gasmi, Mehdi
AU - Bartus, Raymond T.
AU - Kordower, Jeffrey H.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
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
SN - 0969-9961
VL - 26
SP - 375
EP - 384
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -