Long-term Clinical Outcome of Fetal Cell Transplantation for Parkinson Disease

Abstract

IMPORTANCE Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation. OBSERVATIONS Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy. CONCLUSIONS AND RELEVANCE The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.

The role of cell based therapy in the treatment of Parkinson’s disease

“…It has been found that transplantation of the abovementioned tissue can improve movement related problems in PD patients [38]. In a relevant study, it was found that the motor symptoms can improve even for eighteen years after transplantation [39,40]. In addition, some studies exist which showed contradictory results which oppose the above findings [41,42].…”

Imaging in Parkinson's Disease

“…Overall the findings from this study provide the first human evidence for the role of striatal serotonergic ternimals in LIDs pathophysiology and support the development of selective 5-HT 1A agonists for use as antidyskinetic agents in PD. Serotonin terminals are also involved in graft-induced dyskinesias (GIDs), which are involuntary movements when "off" dopaminergic drugs occurring after transplantation of fVM tissue (Kefalopoulou et al, 2014;Politis, Loane, et al, 2011;Politis, Oertel, et al, 2011;Politis, Wu, Loane, Kiferle, et al, 2010;Politis, Wu, Loane, Quinn, et al, 2010;Politis, Wu, Loane, Turkheimer, et al, 2010 PET studies have shown that three PD patients who received striatal transplantation with fVM tissue and exhibited GIDs had excessive graft-derived serotonergic innervation and high serotonin-to-dopamine terminal ratio (Politis, Loane, et al, 2011;Politis, Oertel, et al, 2011;Politis, Wu, Loane, Kiferle, et al, 2010;Politis, Wu, Loane, Quinn, et al, 2010;Politis, Wu, Loane, Turkheimer, et al, 2010). Administration of small, repeated doses of buspirone, was able to attenuate GIDs possibly by attenuating the abnormal serotonin terminal-derived dopamine release (Loane & Politis, 2012;Politis, 2010Politis, , 2011Politis, Loane, et al, 2011;Politis, Oertel, et al, 2011;Politis, Wu, Loane, Kiferle, et al, 2010;Politis, Wu, Loane, Quinn, et al, 2010;Politis, Wu, Loane, Turkheimer, et al, 2010).…”

Transplantation in the nonhuman primate MPTP model of Parkinson's disease: update and perspectives

“…First clinical trials (Lindvall et al, 1988) were again initially promising (Lindvall et al, 1990) but were later held back due to efficiency concerns following studies with a larger number of patients and randomized, double-blind, placebo-controlled protocols (Freed et al, 2001;Olanow et al, 2003) that showed no significant difference between grafted patients and placebo, with several patients developing graft-induced dyskinesia. Nevertheless, retrospective analyses and reports on those clinical trials of fVM striatal grafts demonstrated their efficiency either clinically (Kefalopoulou et al, 2014), histologically (Li et al, 2016), behaviorally (Gordon et al, 2004) or functionally (Politis and Piccini, 2010). Based on all these evidences, a new clinical trial of fVM transplantation has been started on a cohort of patients with improved grafting procedures and selection of patients (Moore et al, 2014) with the aim of preparing for the move to stem-cell-based transplantation in humans while waiting for preclinical investigation reports in animal models.…”