Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys

被引：30

作者：

Daadi, MM

Pivirotto, P

Bringas, J

Cunningham, J

Forsayeth, J

Eberling, J

Bankiewicz, KS

机构：

[1] Parkinsons Inst, Sunnyvale, CA 94089 USA

[2] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA

[3] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA

来源：

NEUROREPORT | 2006年 / 17卷 / 02期

关键词：

gene therapy; long-term gene transfer; monkey MPTR Parkinson's disease; recombinant adeno-associated virus serotype 2; stereology;

D O I：

10.1097/01.wnr.0000198952.38563.05

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 mu l/site of AAV2-hAADC at a concentration of 2 x 10(12)vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC + cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC + cells were neuronal nuclei immunoreactive.

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页码：201 / 204

页数：4

相关论文

共 16 条

[1] Convection-enhanced delivery of AAV vector in parkinsonian monkeys;: In vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach [J].

Bankiewicz, KS ;

Eberling, JL ;

Kohutnicka, M ;

Jagust, W ;

Pivirotto, P ;

Bringas, J ;

Cunningham, J ;

Budinger, TF ;

Harvey-White, J .

EXPERIMENTAL NEUROLOGY, 2000, 164 (01) :2-14

[2] CONVECTION-ENHANCED DELIVERY OF MACROMOLECULES IN THE BRAIN [J].

BOBO, RH ;

LASKE, DW ;

AKBASAK, A ;

MORRISON, PF ;

DEDRICK, RL ;

OLDFIELD, EH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2076-2080

[3] Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system [J].

Burger, C ;

Gorbatyuk, OS ;

Velardo, MJ ;

Peden, CS ;

Williams, P ;

Zolotukhin, S ;

Reier, PJ ;

Mandel, RJ ;

Muzyczka, N .

MOLECULAR THERAPY, 2004, 10 (02) :302-317

[4] Recombinant adeno-associated virus vector: use for transgene expression and anterograde tract tracing in the CNS [J].

Chamberlin, NL ;

Du, B ;

de Lacalle, S ;

Saper, CB .

BRAIN RESEARCH, 1998, 793 (1-2) :169-175

[5] Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors [J].

Fan, DS ;

Ogawa, M ;

Fujimoto, K ;

Ikeguchi, K ;

Ogasawara, Y ;

Urabe, M ;

Nishizawa, M ;

Nakano, I ;

Yoshida, M ;

Nagatsu, I ;

Ichinose, H ;

Nagatsu, T ;

Kurtzman, GJ ;

Ozawa, K .

HUMAN GENE THERAPY, 1998, 9 (17) :2527-2535

[6] Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector [J].

Georgievska, B ;

Kirik, D ;

Rosenblad, C ;

Lundberg, C ;

Björklund, A .

NEUROREPORT, 2002, 13 (01) :75-82

[7]

GUNDERSEN HJG, 1987, J MICROSC-OXFORD, V147, P3

[8] Basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain [J].

Hadaczek, P ;

Mirek, H ;

Bringas, J ;

Cunningham, J ;

Bankiewicz, K .

HUMAN GENE THERAPY, 2004, 15 (05) :469-479

[9] REGULATION OF DOPAMINE PRODUCTION BY GENETICALLY-MODIFIED PRIMARY FIBROBLASTS [J].

KANG, UJ ;

FISHER, LJ ;

JOH, TH ;

OMALLEY, KL ;

GAGE, FH .

JOURNAL OF NEUROSCIENCE, 1993, 13 (12) :5203-5211

[10] Targeted retrograde gene delivery for neuronal protection [J].

Kaspar, BK ;

Erickson, D ;

Schaffer, D ;

Hinh, L ;

Gage, FH ;

Peterson, DA .

MOLECULAR THERAPY, 2002, 5 (01) :50-56