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

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    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 2009

    Fingerprint

    Neurturin
    Corpus Striatum
    Huntington Disease
    Motor Neurons
    Transgenic Mice
    Glial Cell Line-Derived Neurotrophic Factors
    Neurons
    Aptitude
    CERE
    Prefrontal Cortex

    Keywords

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

    ASJC Scopus subject areas

    • Neurology

    Cite this

    Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease. / Ramaswamy, Shilpa; McBride, Jodi; Han, Ina; Berry-Kravis, Elizabeth M.; Zhou, Lili; Herzog, Christopher D.; Gasmi, Mehdi; Bartus, Raymond T.; Kordower, Jeffrey H.

    In: Neurobiology of Disease, Vol. 34, No. 1, 04.2009, p. 40-50.

    Research output: Contribution to journalArticle

    Ramaswamy, Shilpa ; McBride, Jodi ; Han, Ina ; Berry-Kravis, Elizabeth M. ; Zhou, Lili ; Herzog, Christopher D. ; Gasmi, Mehdi ; Bartus, Raymond T. ; Kordower, Jeffrey H. / Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease. In: Neurobiology of Disease. 2009 ; Vol. 34, No. 1. pp. 40-50.
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