Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease

Shilpa Ramaswamy, Jodi L. McBride, Ina Han, Elizabeth M. Berry-Kravis, Lili Zhou, Christopher D. Herzog, Mehdi Gasmi, Raymond T. Bartus, Jeffrey H. Kordower

    Research output: Contribution to journalArticlepeer-review

    42 Scopus citations

    Abstract

    Members of the GDNF family of ligands, including neurturin (NTN), have been implicated as potential therapeutic agents for Huntington's disease (HD). The present study examined the ability of CERE-120 (AAV2-NTN) to provide structural and functional protection in the N171-82Q transgenic HD mouse model. AAV2-NTN therapy attenuated rotorod deficits in this mutant relative to control treated transgenics (p < 0.01). AAV2-NTN treatment significantly reduced the number of transgenic mice that exhibited clasping behavior and partially restored their stride lengths (both p < 0.05). Stereological counts of NeuN-ir neurons revealed a significant neuroprotection in the striatum of AAV2-NTN treated relative to control treated transgenics (p < 0.001). Most fascinating, stereological counts of NeuN-labeled cells in layers V-VI of prefrontal cortex revealed that intrastriatal AAV2-NTN administration prevented the loss of frontal cortical NeuN-ir neurons seen in transgenic mice (p < 0.01). These data indicate that gene delivery of NTN may be a viable strategy for the treatment of this incurable disease.

    Original languageEnglish (US)
    Pages (from-to)40-50
    Number of pages11
    JournalNeurobiology of Disease
    Volume34
    Issue number1
    DOIs
    StatePublished - Apr 1 2009

    Keywords

    • AAV2
    • CERE-120
    • Gene therapy
    • Huntington's disease
    • N171-82Q
    • Neurturin
    • Transgenic mouse model

    ASJC Scopus subject areas

    • Neurology

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