Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation

Abstract

Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.

Cell Therapeutics in Parkinson's Disease

“…To date, immunohistochemical analysis of transplants surviving longer than 10 years has been reported for 5 cases [20,21,[25][26][27]. Consistent with the imaging data, these transplants that had survived for as many as16 years in the brain contained large numbers of dopaminergic neurons (Fig.…”

“…Dopaminergic Grafts Can Survive and Become Morphologically Integrated in the PD Patient's Brain Following implantation of postmitotic DA neuroblasts from the ventral mesencephalon of 6-to 9-weekold human fetuses, positron emission tomography (PET) detected increases in 6-L-[ 18 F]-fluorodopa ( 18 F-dopa) uptake ( Fig. 1) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], and histopathological studies have shown long-term, extensive synaptic reinnervation in the striatum [13,[20][21][22][23][24][25][26][27].…”

Prion-Like Propagation of Protein Aggregation and Related Therapeutic Strategies

“…The patients who came to autopsy after only a few years had clusters of viable dopaminergic neurons that re-innervated areas of the striatum. But after longer incubation periods (12-16 years), α-synuclein and ubiqutin-positive Lewy body pathology was identified in the fetal grafts [25,26]. The presence of metabolically and phenotypically normal dopaminergic grafts early in this process (18 months) suggested a long lag phase before induction of pathology [27][28][29].…”

Dopamine Cell Transplantation for Parkinson's Disease: The Importance of Controlled Clinical Trials

“…Human dopamine cells transplanted and examined postmortem more than a decade after transplant show extensive reinnervation in the putamen [59,61,62,63]. In a small percentage of cells in some centers [61,62], but not others [63], cytoplasmic inclusions resembling Lewy bodies have been observed. Because the overall quality of the dopamine cell transplant and fiber outgrowth remains excellent, the significance of this rare observation is uncertain.…”