Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys.

@article{citeulike:1475894, abstract = {OBJECTIVE: We tested the hypothesis that gene delivery of the trophic factor neurturin could preserve motor function and protect nigrostriatal circuitry in hemiparkinsonian monkeys. METHODS: An adeno-associated virus-based vector encoding human neurturin (AAV2-NTN; also called CERE-120) was injected into the striatum and substantia nigra of monkeys 4 days after a unilateral intracarotid injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rendered them hemiparkinsonian. Control hemiparkinsonian monkeys received either AAV2 encoding green fluorescent protein or formulation buffer. RESULTS: Although stable deficits were seen in all control monkeys, AAV2-NTN significantly improved MPTP-induced motor impairments by 80 to 90\% starting at approximately month 4 and lasting until the end of the experiment (month 10). AAV2-NTN significantly preserved nigral neurons, significantly preserved striatal dopaminergic innervation, and activated phospho-extracellular signal-regulated kinase, consistent with a mechanism involving a trophic factor-initiated molecular cascade. Histological analyses of numerous brain regions, including the cerebellum, showed normal cytoarchitecture and no aberrant pathology. INTERPRETATION: These data demonstrate that AAV2-NTN (CERE-120) can preserve function and anatomy in degenerating nigrostriatal neurons and are supportive of ongoing clinical tests in Parkinson's disease patients.}, address = {Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.}, author = {Kordower, J. H. and Herzog, C. D. and Dass, B. and Bakay, R. A. and Stansell, J. and Gasmi, M. and Bartus, R. T. }, citeulike-article-id = {1475894}, doi = {10.1002/ana.21032}, issn = {0364-5134}, journal = {Ann Neurol}, keywords = {aav, gdnf, monkey, ntn, pd}, month = {December}, number = {6}, pages = {706--715}, posted-at = {2007-07-23 22:18:22}, priority = {2}, title = {Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys.}, url = {http://dx.doi.org/10.1002/ana.21032}, volume = {60}, year = {2006} }

TY - JOUR ID - citeulike:1475894 L3 - citeulike-article-id:1475894 TI - Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. JF - Ann Neurol VL - 60 IS - 6 SP - 706 EP - 715 AD - Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. SN - 0364-5134 N2 - OBJECTIVE: We tested the hypothesis that gene delivery of the trophic factor neurturin could preserve motor function and protect nigrostriatal circuitry in hemiparkinsonian monkeys. METHODS: An adeno-associated virus-based vector encoding human neurturin (AAV2-NTN; also called CERE-120) was injected into the striatum and substantia nigra of monkeys 4 days after a unilateral intracarotid injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rendered them hemiparkinsonian. Control hemiparkinsonian monkeys received either AAV2 encoding green fluorescent protein or formulation buffer. RESULTS: Although stable deficits were seen in all control monkeys, AAV2-NTN significantly improved MPTP-induced motor impairments by 80 to 90% starting at approximately month 4 and lasting until the end of the experiment (month 10). AAV2-NTN significantly preserved nigral neurons, significantly preserved striatal dopaminergic innervation, and activated phospho-extracellular signal-regulated kinase, consistent with a mechanism involving a trophic factor-initiated molecular cascade. Histological analyses of numerous brain regions, including the cerebellum, showed normal cytoarchitecture and no aberrant pathology. INTERPRETATION: These data demonstrate that AAV2-NTN (CERE-120) can preserve function and anatomy in degenerating nigrostriatal neurons and are supportive of ongoing clinical tests in Parkinson's disease patients. KW - aav KW - gdnf KW - monkey KW - ntn KW - pd AU - Kordower, JH AU - Herzog, CD AU - Dass, B AU - Bakay, RA AU - Stansell, J AU - Gasmi, M AU - Bartus, RT PY - 2006/12// UR - http://dx.doi.org/10.1002/ana.21032 ER -