Porcine Embryonic Xenografts Transgenic for CTLA4-Ig Enable Longterm Recovery in Parkinsonian Macaques

Neural transplantation has been attempted as a therapeutic approach in Parkinson’s disease (PD) with variable outcomes. Here we evaluated a novel strategy for long term survival, maturation and functional recovery of intrastriatal implantation of mesencephalic dopaminergic-enriched porcine grafts in PD primates. Methods PD was induced in 11 macaques using MPTP. PD monkeys were injected into the left putamen with cells from the ventral mesencephalon of CTLA4-Ig+ pig embryos (E27) and were immunosuppressed with a clinical immunosuppressive regimen (cyclosporin A, mycophenolate and steroids). Xenograft survival and function was determined by neurological assessments, analysis of locomotor function (Ethovision software), brain imaging (PET scan with 18F-L-DOPA), and histology. Results Xenografted animals were monitored for up to 320 days (2 longterm recipients still alive). A significant recovery of locomotion was observed in all animals for up to 11 months post transplantation, most probably due to partial restoration of dopaminergic activity detected by PET scans. Histology of the brain revealed large porcine grafts composed of dopaminergic, serotoninergic and GABAergic differentiated neurons and glial components. Conclusion These studies demonstrate that transplantation of CTLA4-Ig porcine embryonic grafts in immunosuppressed PD primates enable longterm xenograft survival and differentiation, associated with significant improvement of locomotor activity.