PT  - JOURNAL ARTICLE
AU  - Adrian P. Kells
AU  - Jamie Eberling
AU  - Xiaomin Su
AU  - Philip Pivirotto
AU  - John Bringas
AU  - Piotr Hadaczek
AU  - Wade C. Narrow
AU  - William J. Bowers
AU  - Howard J. Federoff
AU  - John Forsayeth
AU  - Krystof S. Bankiewicz
TI  - Regeneration of the MPTP-Lesioned Dopaminergic System after Convection-Enhanced Delivery of AAV2-GDNF
AID  - 10.1523/JNEUROSCI.0942-10.2010
DP  - 2010 Jul 14
TA  - The Journal of Neuroscience
PG  - 9567--9577
VI  - 30
IP  - 28
4099  - http://www.jneurosci.org/content/30/28/9567.short
4100  - http://www.jneurosci.org/content/30/28/9567.full
SO  - J. Neurosci.2010 Jul 14; 30
AB  - Clinical studies to date have failed to establish therapeutic benefit of glial cell-derived neurotrophic factor (GDNF) in Parkinson's disease (PD). In contrast to previous nonclinical neuroprotective reports, this study shows clinically relevant and long-lasting regeneration of the dopaminergic system in rhesus macaques lesioned with 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine 3–6 months before GDNF gene delivery (AAV2-GDNF). The observed progressive amelioration of functional deficits, recovery of dopamine, and regrowth of fibers to the striatal neuropil demonstrate that high GDNF expression in the putamen promotes restoration of the dopaminergic system in a primate model of advanced PD. Extensive distribution of GDNF within the putamen and transport to the severely lesioned substantia nigra, after convection-enhanced delivery of AAV2-GDNF into the putamen, indicates anterograde transport via striatonigral connections and is anticipated to occur in PD patients. Overall, these data demonstrate nonclinical neurorestoration after putaminal infusion of AAV2-GDNF and suggest that clinical investigation in PD patients is warranted.