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Neural Plasticity
Volume 2019, Article ID 6286197, 9 pages
https://doi.org/10.1155/2019/6286197
Research Article

Widespread Striatal Delivery of GDNF from Encapsulated Cells Prevents the Anatomical and Functional Consequences of Excitotoxicity

1Gloriana Therapeutics, Providence, Rhode Island, USA
2Department of Neurological Sciences, Rush University Medical Center, Chicago Illinois, USA
3Cytosolv, Providence, Rhode Island, USA
4Department of Diagnostic and Public Health, Section of Pharmacology, University of Verona P.le, LA Scuro, Verona, Italy

Correspondence should be addressed to Dwaine F. Emerich; moc.xtanairolg@efd

Received 9 November 2018; Accepted 11 February 2019; Published 11 March 2019

Guest Editor: Jolanta Dorszewska

Copyright © 2019 Dwaine F. Emerich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Methods. Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a battery of validated motor tests, and histology was performed to determine the extent of GDNF diffusion and associated prevention of neuronal cell loss and behavioral deficits. Results. Encapsulated cell-based delivery of GDNF produced widespread distribution of GDNF throughout the entire implanted striatum. Stereological estimates of striatal neuron number and volume of lesion size revealed that GDNF delivery resulted in near complete neuroprotection. Conclusions. Delivery of neurotrophic molecules such as GDNF using encapsulated cells has reached a technological point where clinical evaluation is justified. Because GDNF has been effective in animal models of Parkinson’s disease, stroke, epilepsy, and Huntington’s disease, among other debilitating neurodegenerative diseases, encapsulated cell-based delivery of GDNF might represent one innovative means of slowing the neural degeneration seen in a myriad of currently untreatable neurological diseases.