title: Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease.
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.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Ramaswamy
authors.forename: Jodi L
authors.initials: JL
authors.lastname: McBride
authors.forename: Ina
authors.initials: I
authors.lastname: Han
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Herzog
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gasmi
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Bartus
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Kordower
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology*; D004268:DNA-Binding Proteins; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D051101:Neurturin / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D045442:Rotarod Performance Test
chemical_list: D004268:DNA-Binding Proteins; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D051101:Neurturin; D009687:Nuclear Proteins