Long-term, stable, targeted biodelivery and efficacy of GDNF from encapsulated cells in the rat and Goettingen miniature pig brain

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.