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

Dwaine F Emerich, Jeffrey H Kordower, Yaping Chu, Chris Thanos, Briannan Bintz, Giovanna Paolone, Lars U Wahlberg

Neural Plast. 2019 Mar 11;2019:6286197.

PMID: 30984255

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248828 GDNF from rat GDNF from rat Price
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