Abstract
Delivering glial cell line-derived neurotrophic factor (GDNF) to the brain is a potential treatment for Parkinson's Disease (PD). Here we use an implantable encapsulated cell technology that uses modified human clonal ARPE-19 cells to deliver of GDNF to the brain. In vivo studies demonstrated sustained delivery of GDNF to the rat striatum over 6 months. Anatomical benefits and behavioral efficacy were shown in 6-OHDA lesioned rats where nigral dopaminergic neurons were preserved in neuroprotection studies and dopaminergic fibers were restored in neurorecovery studies. When larger, clinical-sized devices were implanted for 3 months into the putamen of Göttingen minipigs, GDNF was widely distributed throughout the putamen and caudate producing a significant upregulation of tyrosine hydroxylase immunohistochemistry. These results are the first to provide clear evidence that implantation of encapsulated GDNF-secreting cells deliver efficacious and biologically relevant amounts of GDNF in a sustained and targeted manner that is scalable to treat the large putamen in patients with Parkinson's disease.
Original language | English (US) |
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Pages (from-to) | 19-29 |
Number of pages | 11 |
Journal | Current Research in Pharmacology and Drug Discovery |
Volume | 1 |
DOIs | |
State | Published - Apr 2020 |
Externally published | Yes |
Keywords
- Encapsulation
- GDNF
- Neuroprotection
- Neuroregeneration
ASJC Scopus subject areas
- Animal Science and Zoology
- Ecology, Evolution, Behavior and Systematics