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

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• 作者：Shilpa Ramaswamy ; Jodi L. McBride ; Ina Han ; Elizabeth M. Berry-Kravis ; Lili Zhou ; Christopher D. Herzog ; Mehdi Gasmi ; Raymond T. Bartus ; Jeffrey H. Kordower
• 关键词：Huntington's disease ; N171-82Q ; Neurturin ; CERE-120 ; Gene therapy ; Transgenic mouse model ; AAV2
• 刊名：Neurobiology of Disease
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：34
• 期：1
• 页码：40-50
• 全文大小：969 K

文摘

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.