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

• Main Authors: Shilpa Ramaswamy, Jodi L. McBride, Ina Han, Elizabeth M. Berry-Kravis, Lili Zhou, Christopher D. Herzog, Mehdi Gasmi, Raymond T. Bartus, Jeffrey H. Kordower
• Format: Article
• Language: English
• Published: Elsevier 2009-04-01
• Series: Neurobiology of Disease
• Subjects: Huntington's disease; N171-82Q; Neurturin; CERE-120; Gene therapy; Transgenic mouse model
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996108003094
• ISSN: 1095-953X

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.