Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
A P KellsK S Bankiewicz

Abstract

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.

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Citations

May 24, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Waldy San SebastianKrystof S Bankiewicz
Nov 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Agnieszka CiesielskaKrystof S Bankiewicz
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May 20, 2020·Expert Review of Neurotherapeutics·Aristide MerolaKrzysztof Bankiewicz

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