Objective: To characterize clinical and radiological outcomes in 4 patients with Parkinson’s disease (PD) at 16-18 years post-transplant of fetal ventral mesencephalic (fVM) tissue into the bilateral putamen.

Background: It is critical to understand outcomes of previous attempts at cell replacement in light of current efforts to develop novel stem cell technologies for neurorestoration. Despite a rich history of fVM tissue allotransplantation, there is a dearth of data on very long term outcomes.

Methods: We enrolled 4 patients who received bilateral putamen fVM tissue transplant in a rigorous sham surgery-controlled clinical trial (Freed et al 2001) to undergo: (1) comprehensive motor and non-motor testing (n=4), (2) ¹¹C-PE2i positron emission tomography (PET) imaging of the dopamine transporter (n=3), and (3) accelerometry-based monitoring (n=2).

Results: Subject ages were 59, 62, 75, and 72 years with PD onset at 24, 34, 44 and 36 years respectively. LRRK2 mutations were present in patients 3 and 4. All underwent fVM transplantation 16-18 years ago, with later DBS undertaken in all, and pallidotomy in patient 2. At the time of our study, medications ranged from 300mg (patient 1) to 1260mg (patient 4) levodopa equivalents daily. Patients 1 and 2 could walk unassisted and live independently. Graft-induced dyskinesias were recorded in the “off medication, off stimulation” state in patients 1 and 2, and to a lesser degree, patient 3. MoCA scores were 25 (patients 3 and 4) and 27 (patients 1 and 2). ¹¹C-PE2i PET imaging strongly suggested maintenance of engrafted tissue with irregular borders in the 3 patients undergoing neuroimaging (patients 1,2,4). Video-recorded exams, detailed motor, cognitive, and other non-motor outcomes including neuropsychological testing and accelerometry-based recordings are presented.

Conclusions: Clinical and neuroimaging outcomes at 16-18 years post-fVM transplant for PD in 4 patients support: (1) evidence of graft maintenance (2) clinically manifest graft activity in a subset, and (3) heterogeneous yet atypical outcomes at PD duration up to 36 years. With current intense interest in neuroregenerative approaches, careful attention to long term outcomes of previous transplant trials should aid in crafting future trial design.

Abstract submitted to 68th AAN Annual Meeting 2016: Very Long Term Clinical and Radiological Outcomes of Fetal Tissue Transplant for Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-neuroimaging-outcomes-up-to-18-years-after-fetal-tissue-transplant-for-parkinsons-disease/