Long-term outcome of unilaterally transplanted parkinsonian patients

Abstract

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n=1) or putamen and caudate (n=4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in the fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed, starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A mild to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed, whereas, apart from one case, no other clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period, all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively, it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter, to reduce the dose of L-dopa.

Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

“…This highlights the fact that striatal cell transplantation can offer a substantial clinical benefit also in moderate to severe PD patients, as has been recently reported in an open label study (Mendez et al, 2005). It is also worth noting that these functional benefits were achieved with only unilateral striatal transplantation, in a bilateral PD primate model, similar to cases in clinical studies of fetal transplantation (Defer et al, 1996;Lindvall et al, 1994;Mendez et al, 2005;Piccini et al, 1999), unilateral striatal GDNF infusion (Slevin et al, 2007;Slevin et al, 2005), and DBS stimulation (Slowinski et al, 2007). In these previous reports, bilateral functional benefit included mild to moderate ipsilateral and axial improvements and a pronounced contralateral improvements (Bastian et al, 2003;Germano et al, 2004), although the magnitude of ipsilateral and axial changes was not studied in detail.…”

Immune response after striatal engraftment of fetal neuronal cells in patients with Huntington’s disease: Consequences for cerebral transplantation programs

“…Studies investigating the safety and efficacy of transplanted neuronal tissue in the past have generated little consensus about the need and the duration of immunosuppressant treatment. Post-graft immunosuppressive treatments have been extremely diverse, ranging from long-term classical triple therapy 10,11 to no treatment at all. 6 There is now a general consensus about a timely limited need for immunosuppressive regimens after intracerebral neural grafts comparable to those used in other cases of allotransplantation.…”

Serotonin Neuron Transplants Exacerbate l-DOPA- Induced Dyskinesias in a Rat Model of Parkinson's Disease

“…The results have been highly variable, with some patients showing a substantial recovery in motor function, and others showing little or no improvement. In open-label trials, a significant reduction in peak dose dyskinesias ("on" time with dyskinesias) has been reported in some patients, whereas in others the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesias have been unaffected or increased (Widner et al, 1992;Defer et al, 1996;Hagell et al, 1999;Hauser et al, 1999;Brundin et al, 2000). These discrepancies have been suggested, at least in part, to be attributable to the differences in dissection and preparation of the fetal tissue, in which tissue clumps, tissue stripes, or single-cell suspensions have been used (Winkler et al, 2005).…”