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

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neurology

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