Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 7 February 1997:
Vol. 275. no. 5301, pp. 838 - 841
DOI: 10.1126/science.275.5301.838
Prev | Table of Contents | Next

Reports

Dopaminergic Neurons Protected from Degeneration by GDNF Gene Therapy

Derek L. Choi-Lundberg, Qing Lin, Yung-Nien Chang, Yawen L. Chiang, Carl M. Hay, Hasan Mohajeri, Beverly L. Davidson, Martha C. Bohn *

Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.

D. L. Choi-Lundberg, Q. Lin, H. Mohajeri, M. C. Bohn, Department of Neurobiology and Anatomy, University of Rochester, Box B603, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Y.-N. Chang, Y. L. Chiang, C. M. Hay, Genetic Therapy, 19 First Field Road, Gaithersburg, MD 20878, USA.
B. L. Davidson, Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
*   To whom correspondence should be addressed. E-mail: mbohn{at}troi.cc.rochester.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Glial Cell Line-derived Neurotrophic Factor Reverses Ethanol-mediated Increases in Tyrosine Hydroxylase Immunoreactivity via Altering the Activity of Heat Shock Protein 90.
D.-Y. He and D. Ron (2008)
J. Biol. Chem. 283, 12811-12818
   Abstract »    Full Text »    PDF »
MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector.
Y.-H. Chen, B. K. Harvey, A. F. Hoffman, Y. Wang, Y.-H. Chiang, and C. R. Lupica (2008)
FASEB J 22, 261-275
   Abstract »    Full Text »    PDF »
RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals.
S. Kowsky, C. Poppelmeyer, E. R. Kramer, B. H. Falkenburger, A. Kruse, R. Klein, and J. B. Schulz (2007)
PNAS 104, 20049-20054
   Abstract »    Full Text »    PDF »
From the Cover: Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells.
D. E. Redmond Jr., K. B. Bjugstad, Y. D. Teng, V. Ourednik, J. Ourednik, D. R. Wakeman, X. H. Parsons, R. Gonzalez, B. C. Blanchard, S. U. Kim, et al. (2007)
PNAS 104, 12175-12180
   Abstract »    Full Text »    PDF »
Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial cell line-derived neurotrophic factor mutant mice.
Y. Yan, K. Yamada, M. Niwa, T. Nagai, A. Nitta, and T. Nabeshima (2007)
FASEB J 21, 1994-2004
   Abstract »    Full Text »    PDF »
A specific survival response in dopamine neurons at most risk in Parkinson's disease..
S. Murase and R. D. McKay (2006)
J. Neurosci. 26, 9750-9760
   Abstract »    Full Text »    PDF »
Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease.
J. L. McBride, S. Ramaswamy, M. Gasmi, R. T. Bartus, C. D. Herzog, E. P. Brandon, L. Zhou, M. R. Pitzer, E. M. Berry-Kravis, and J. H. Kordower (2006)
PNAS 103, 9345-9350
   Abstract »    Full Text »    PDF »
Gene transfer of trophic factors and stem cell grafting as treatments for Parkinson's disease.
B. Dass, C. W. Olanow, and J. H. Kordower (2006)
Neurology 66, S89-S103
   Abstract »    Full Text »
Substance P, Neurokinins A and B, and Synthetic Tachykinin Peptides Protect Mesencephalic Dopaminergic Neurons in Culture via an Activity-Dependent Mechanism.
B. Salthun-Lassalle, S. Traver, E. C. Hirsch, and P. P. Michel (2005)
Mol. Pharmacol. 68, 1214-1224
   Abstract »    Full Text »    PDF »
Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body Cells In Situ and after Intrastriatal Transplantation.
J. Villadiego, S. Mendez-Ferrer, T. Valdes-Sanchez, I. Silos-Santiago, I. Farinas, J. Lopez-Barneo, and J. J. Toledo-Aral (2005)
J. Neurosci. 25, 4091-4098
   Abstract »    Full Text »    PDF »
Continuous Low-Level Glial Cell Line-Derived Neurotrophic Factor Delivery Using Recombinant Adeno-Associated Viral Vectors Provides Neuroprotection and Induces Behavioral Recovery in a Primate Model of Parkinson's Disease.
A. Eslamboli, B. Georgievska, R. M. Ridley, H. F. Baker, N. Muzyczka, C. Burger, R. J. Mandel, L. Annett, and D. Kirik (2005)
J. Neurosci. 25, 769-777
   Abstract »    Full Text »    PDF »
Overexpression of Glial Cell Line-Derived Neurotrophic Factor Using a Lentiviral Vector Induces Time- and Dose-Dependent Downregulation of Tyrosine Hydroxylase in the Intact Nigrostriatal Dopamine System.
B. Georgievska, D. Kirik, and A. Bjorklund (2004)
J. Neurosci. 24, 6437-6445
   Abstract »    Full Text »    PDF »
Transduction Profiles of Recombinant Adeno-Associated Virus Vectors Derived from Serotypes 2 and 5 in the Nigrostriatal System of Rats.
J.-C. Paterna, J. Feldon, and H. Bueler (2004)
J. Virol. 78, 6808-6817
   Abstract »    Full Text »    PDF »
Rescue of Mesencephalic Dopaminergic Neurons in Culture by Low-Level Stimulation of Voltage-Gated Sodium Channels.
B. Salthun-Lassalle, E. C. Hirsch, J. Wolfart, M. Ruberg, and P. P. Michel (2004)
J. Neurosci. 24, 5922-5930
   Abstract »    Full Text »    PDF »
Regulation of the Development of Mesencephalic Dopaminergic Systems by the Selective Expression of Glial Cell Line-Derived Neurotrophic Factor in Their Targets.
N. Kholodilov, O. Yarygina, T. F. Oo, H. Zhang, D. Sulzer, W. Dauer, and R. E. Burke (2004)
J. Neurosci. 24, 3136-3146
   Abstract »    Full Text »    PDF »
Gene Transfer to the Nervous System: Prospects for Novel Treatments Directed at Diseases of the Aging Nervous System.
M. Mata, J. C. Glorioso, and D. J. Fink (2003)
J. Gerontol. A Biol. Sci. Med. Sci. 58, M1111-1118
   Abstract »    Full Text »    PDF »
Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together.
D. W Munno and N. I Syed (2003)
J. Physiol. 552, 1-11
   Abstract »    Full Text »    PDF »
The binding of human glial cell line-derived neurotrophic factor to heparin and heparan sulfate: importance of 2-O-sulfate groups and effect on its interaction with its receptor, GFR{alpha}1.
S. M. Rickard, R. S. Mummery, B. Mulloy, and C. C. Rider (2003)
Glycobiology 13, 419-426
   Abstract »    Full Text »    PDF »
Trophic Restoration of the Nigrostriatal Dopaminergic Pathway in Long-Term Carotid Body-Grafted Parkinsonian Rats.
J. J. Toledo-Aral, S. Mendez-Ferrer, R. Pardal, M. Echevarria, and J. Lopez-Barneo (2003)
J. Neurosci. 23, 141-148
   Abstract »    Full Text »    PDF »
Book Review: Cellular Replacement Therapy for Parkinson's Disease--Where We Are Today?.
D. E. Redmond Jr. (2002)
Neuroscientist 8, 457-488
   Abstract »    PDF »
Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys.
R. Grondin, Z. Zhang, A. Yi, W. A. Cass, N. Maswood, A. H. Andersen, D. D. Elsberry, M. C. Klein, G. A. Gerhardt, and D. M. Gash (2002)
Brain 125, 2191-2201
   Abstract »    Full Text »    PDF »
Lentivirally Delivered Glial Cell Line-Derived Neurotrophic Factor Increases the Number of Striatal Dopaminergic Neurons in Primate Models of Nigrostriatal Degeneration.
S. Palfi, L. Leventhal, Y. Chu, S. Y. Ma, M. Emborg, R. Bakay, N. Deglon, P. Hantraye, P. Aebischer, and J. H. Kordower (2002)
J. Neurosci. 22, 4942-4954
   Abstract »    Full Text »    PDF »
Effect of GDNF on Neuroblast Proliferation and Photoreceptor Survival: Additive Protection with Docosahexaenoic Acid.
L. E. Politi, N. P. Rotstein, and N. G. Carri (2001)
Invest. Ophthalmol. Vis. Sci. 42, 3008-3015
   Abstract »    Full Text »    PDF »
Neuroprotection through Delivery of Glial Cell Line-Derived Neurotrophic Factor by Neural Stem Cells in a Mouse Model of Parkinson's Disease.
P. Akerud, J. M. Canals, E. Y. Snyder, and E. Arenas (2001)
J. Neurosci. 21, 8108-8118
   Abstract »    Full Text »    PDF »
Protection by Synergistic Effects of Adenovirus-Mediated X-Chromosome-Linked Inhibitor of Apoptosis and Glial Cell Line-Derived Neurotrophic Factor Gene Transfer in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease.
O. Eberhardt, R. V. Coelln, S. Kugler, J. Lindenau, S. Rathke-Hartlieb, E. Gerhardt, S. Haid, S. Isenmann, C. Gravel, A. Srinivasan, et al. (2000)
J. Neurosci. 20, 9126-9134
   Abstract »    Full Text »    PDF »
Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in Primate Models of Parkinson's Disease.
J. H. Kordower, M. E. Emborg, J. Bloch, S. Y. Ma, Y. Chu, L. Leventhal, J. McBride, E.-Y. Chen, S. Palfi, B. Z. Roitberg, et al. (2000)
Science 290, 767-773
   Abstract »    Full Text »
Exploiting Nonneural Cells to Rebuild the Nervous System: From Bone Marrow to Brain.
S. A. Azizi (2000)
Neuroscientist 6, 353-361
   Abstract »    PDF »
Complete and Long-Term Rescue of Lesioned Adult Motoneurons by Lentiviral-Mediated Expression of Glial Cell Line-Derived Neurotrophic Factor in the Facial Nucleus.
A. F. Hottinger, M. Azzouz, N. Deglon, P. Aebischer, and A. D. Zurn (2000)
J. Neurosci. 20, 5587-5593
   Abstract »    Full Text »    PDF »
Extensive Sprouting of Sensory Afferents and Hyperalgesia Induced by Conditional Expression of Nerve Growth Factor in the Adult Spinal Cord.
M. I. Romero, N. Rangappa, L. Li, E. Lightfoot, M. G. Garry, and G. M. Smith (2000)
J. Neurosci. 20, 4435-4445
   Abstract »    Full Text »    PDF »
Long-Term rAAV-Mediated Gene Transfer of GDNF in the Rat Parkinson's Model: Intrastriatal But Not Intranigral Transduction Promotes Functional Regeneration in the Lesioned Nigrostriatal System.
D. Kirik, C. Rosenblad, A. Bjorklund, and R. J. Mandel (2000)
J. Neurosci. 20, 4686-4700
   Abstract »    Full Text »    PDF »
Gene transfer of calcitonin gene-related peptide to cerebral arteries.
K. Toyoda, F. M. Faraci, A. F. Russo, B. L. Davidson, and D. D. Heistad (2000)
Am J Physiol Heart Circ Physiol 278, H586-H594
   Abstract »    Full Text »    PDF »
Mind Glue: Implications of Glial Cell Biology for Psychiatry.
J. T. Coyle and R. Schwarcz (2000)
Arch Gen Psychiatry 57, 90-93
   Full Text »    PDF »
Gene therapy using viral vectors for acute neurologic insults.
R. M. Sapolsky and G. K. Steinberg (1999)
Neurology 53, 1922
   Abstract »    Full Text »    PDF »
Glial Cell Line-Derived Neurotrophic Factor Induces Histologic and Functional Protection of Rod Photoreceptors in the rd/rd Mouse.
M. Frasson, S. Picaud, T. Leveillard, M. Simonutti, S. Mohand-Said, H. Dreyfus, D. Hicks, and J. Sahel (1999)
Invest. Ophthalmol. Vis. Sci. 40, 2724-2734
   Abstract »    Full Text »    PDF »
Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo.
M. Yamada, T. Oligino, M. Mata, J. R. Goss, J. C. Glorioso, and D. J. Fink (1999)
PNAS 96, 4078-4083
   Abstract »    Full Text »    PDF »
Group D Adenoviruses Infect Primary Central Nervous System Cells More Efficiently than Those from Group C.
M. Chillon, A. Bosch, J. Zabner, L. Law, D. Armentano, M. J. Welsh, and B. L. Davidson (1999)
J. Virol. 73, 2537-2540
   Abstract »    Full Text »
GDNF Protection against 6-OHDA-Induced Reductions in Potassium-Evoked Overflow of Striatal Dopamine.
W. A. Cass and M. W. Manning (1999)
J. Neurosci. 19, 1416-1423
   Abstract »    Full Text »    PDF »
Interleukin-1 Mediates a Rapid Inflammatory Response After Injection of Adenoviral Vectors into the Brain.
T. Cartmell, T. Southgate, G. S. Rees, M. G. Castro, P. R. Lowenstein, and G. N. Luheshi (1999)
J. Neurosci. 19, 1517-1523
   Abstract »    Full Text »    PDF »
Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system.
S Taraviras, C. Marcos-Gutierrez, P Durbec, H Jani, M Grigoriou, M Sukumaran, L. Wang, M Hynes, G Raisman, and V Pachnis (1999)
Development 126, 2785-2797
   Abstract »    PDF »
Herpes Simplex Virus Type 1 Vector-Mediated Expression of Nerve Growth Factor Protects Dorsal Root Ganglion Neurons from Peroxide Toxicity.
W. F. Goins, K. A. Lee, J. D. Cavalcoli, M. E. O'Malley, S. T. DeKosky, D. J. Fink, and J. C. Glorioso (1999)
J. Virol. 73, 519-532
   Abstract »    Full Text »    PDF »
Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons.
O. Saucedo-Cardenas, J. D. Quintana-Hau, W.-D. Le, M. P. Smidt, J. J. Cox, F. De Mayo, J. P. H. Burbach, and O. M. Conneely (1998)
PNAS 95, 4013-4018
   Abstract »    Full Text »    PDF »
Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats.
R. J. Mandel, S. K. Spratt, R. O. Snyder, and S. E. Leff (1997)
PNAS 94, 14083-14088
   Abstract »    Full Text »    PDF »
GDNF Protection against 6-OHDA: Time Dependence and Requirement for Protein Synthesis.
C. M. Kearns, W. A. Cass, K. Smoot, R. Kryscio, and D. M. Gash (1997)
J. Neurosci. 17, 7111-7118
   Abstract »    Full Text »    PDF »
Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.
A. Bilang-Bleuel, F. Revah, P. Colin, I. Locquet, J.-J. Robert, J. Mallet, and P. Horellou (1997)
PNAS 94, 8818-8823
   Abstract »    Full Text »    PDF »
Experiments in a Parkinson's Rat Model.
R. Pallini, A. Consales, L. Lauretti, E. Fernandez;, D. L. Choi-Lundberg, and M. C. Bohn; (1997)
Science 277, 389-390
   Full Text »
Tetrahydrobiopterin Enhances Apoptotic PC12 Cell Death following Withdrawal of Trophic Support.
P. Z. Anastasiadis, H. Jiang, L. Bezin, D. M. Kuhn, and R. A. Levine (2001)
J. Biol. Chem. 276, 9050-9058
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)