Intranasal Delivery of pGDNF DNA Nanoparticles Provides Neuroprotection in the Rat 6-Hydroxydopamine Model of Parkinson's Disease

Molecular Neurobiology
Amirah E-E AlyBarbara L Waszczak

Abstract

Glial cell line-derived neurotrophic factor (GDNF) gene therapy could offer a disease-modifying treatment for Parkinson's disease (PD). Here, we report that plasmid DNA nanoparticles (NPs) encoding human GDNF administered intranasally to rats induce transgene expression in the brain and protect dopamine neurons in a model of PD. To first test whether intranasal administration could transfect cells in the brain, rats were sacrificed 1 week after intranasal pGDNF NPs or the naked plasmid. GDNF ELISA revealed significant increases in GDNF expression throughout the brain for both treatments. To assess whether expression was sufficient to protect dopamine neurons, naked pGDNF and pGDNF DNA NPs were given intranasally 1 week before a unilateral 6-hydroxydopamine lesion in a rat model of PD. Three to four weeks after the lesion, amphetamine-induced rotational behavior was reduced, and dopaminergic fiber density and cell counts in the lesioned substantia nigra and nerve terminal density in the lesioned striatum were significantly preserved in rats given intranasal pGDNF. The NPs afforded a greater level of neuroprotection than the naked plasmid. These results provide proof-of-principle that intranasal administration of pGDNF DNA NPs ca...Continue Reading

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Citations

Apr 14, 2019·The Journal of Gene Medicine·Shanshan Wang, Rongqin Huang
Jan 7, 2020·Current Drug Metabolism·Pooja MalaviyaAbhay R Vasavada
May 15, 2020·Experimental Neurobiology·Dongyoung YunSang Ryong Kim
May 20, 2020·Expert Review of Neurotherapeutics·Aristide MerolaKrzysztof Bankiewicz
Apr 7, 2020·Biotechnology and Applied Biochemistry·AmirHossein BahmanpourMasoud Mozafari
Jul 3, 2020·Chemical & Pharmaceutical Bulletin·Koki OgawaShigeru Kawakami
Sep 20, 2020·Biomolecules·Loredana LeggioNunzio Iraci
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Oct 9, 2020·Advanced Drug Delivery Reviews·Aroa Duro-CastanoGiuseppe Battaglia
Nov 18, 2020·Trends in Pharmacological Sciences·Yulia A Sidorova, Mart Saarma

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Methods Mentioned

BETA
transfect
transfection
ELISA
ELISAs
protein
pharmacotherapies

Software Mentioned

BIOQUANT®
GraphPad Prism®
NIH ImageJ
CellCounter
GraphPad Prism
Gen5®

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