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 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.
Ramaswamy
Shilpa
S
Department of Neuroscience, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USA.
McBride
Jodi L
JL
Herzog
Christopher D
CD
Brandon
Eugene
E
Gasmi
Mehdi
M
Bartus
Raymond T
RT
Kordower
Jeffrey H
JH
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019610:Cytoprotection / Q000235:genetics; D004268:DNA-Binding Proteins; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques / Q000639:trends; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006816:Huntington Disease / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D008297:Male; D009043:Motor Activity / Q000235:genetics; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins; D051101:Neurturin / Q000235:genetics* / Q000627:therapeutic use; D009574:Nitro Compounds; D009687:Nuclear Proteins / Q000378:metabolism; D011422:Propionates; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000235:genetics; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009498:Neurotoxins; D051101:Neurturin; D009574:Nitro Compounds; C495057:Nrtn protein, rat; D009687:Nuclear Proteins; D011422:Propionates; C015392:3-nitropropionic acid