Very Long Term Clinical and Radiological Outcomes of Fetal Tissue Transplant for Parkinsons Disease (P3.358)

OBJECTIVE: To characterize very long term outcomes in patients with Parkinsons disease (PD) after bilateral intraputamenal fetal ventral mesencephalic (fVM) tissue transplant. BACKGROUND: Neurorestorative approaches to PD based upon radically new stem cell technologies are imminent, and it is critical to understand outcomes of previous attempts at cell-based transplantation. Allotransplant of dopaminergic neuroblasts in fetal mesencephalic tissue is the best-studied reparative PD intervention, but long-term outcomes are almost entirely unreported. DESIGN/METHODS: We enrolled patients who underwent fVM tissue transplant to the bilateral putamen in a rigorous sham surgery controlled clinical trial (Freed et al 2001). To date, two patients have undergone (1) clinical batteries comprising detailed motor and non-motor measures, and (2) 11C-PE2i positron emission tomography (PET) imaging targeting the dopamine transporter. RESULTS: Patients 1 and 2 (onset 24 and 34 years old) underwent fVM transplantation at 12 and 17 years disease duration. Both subsequently underwent bilateral STN DBS, and patient 2 underwent right pallidotomy. At 16 years post-transplant, change in motor Unified Parkinsons Disease Rating Scale (UPDRS) in the off state was from 45 to 55 points (patient 1) and from 34 to 43 points (patient 2), despite minimal anti-PD medications. Both had graft-induced dyskinesias as evidenced in the off medication, off stimulation state. 11C-PE2i PET imaging strongly suggested maintenance of engrafted tissue with irregular borders. Further results including non-motor symptoms, genetic analysis and an expanded patient cohort will be presented. CONCLUSIONS: This is the first report of very long term clinical and neuroimaging outcomes of two patients who underwent fVM transplant for PD. Our data support graft maintenance and function at 16 years post transplant. At a time of resurgence of interest in neuroregenerative approaches for PD this extensive follow up supports cell transplantation approaches but points to potential limitations and areas for continued focus for the field. Disclosure: Dr Henchcliffe has received research support from Kaneka and Biogen. Dr. Carter has nothing to disclose. Dr. Kang has nothing to disclose. Dr. Babich has nothing to disclose. Dr. Ravdin has nothing to disclose. Dr. Gollomp has received research support for activities with Kyowa Pharmaceuticals, Allergan, Novartis, and Eisai. Dr. Strafella has nothing to disclose. Dr. Fasano has received personal compensation for activities with Abbvie, Boston Scientific, Medtronic, Teva, and UCB Pharma. Dr. Hellmers has nothing to disclose. Dr. McRae has nothing to disclose.