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'sDisease (PD). Here we use an implantable encapsulated cell technology that uses modified human clonal ARPE-19cells to deliver of GDNF to the brain. In vivostudies demonstrated sustained delivery of GDNF to the rat striatumover 6 months. Anatomical benefits and behavioral efficacy were shown in 6-OHDA lesioned rats where nigraldopaminergic neurons were preserved in neuroprotection studies and dopaminergicfibers were restored inneurorecovery studies. When larger, clinical-sized devices were implanted for 3 months into the putamen ofG€ottingen minipigs, GDNF was widely distributed throughout the putamen and caudate producing a significantupregulation of tyrosine hydroxylase immunohistochemistry. These results are thefirst to provide clear evidencethat implantation of encapsulated GDNF-secreting cells deliver efficacious and biologically relevant amounts ofGDNF in a sustained and targeted manner that is scalable to treat the large putamen in patients with Parkinson'sdisease