Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease

Abstract

We performed fetal nigral transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the "off" state, Schwab-England disability score during the "off" state, percent "off" time, and percent "on" time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following fetal tissue transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

“…Neural transplantation of fetal ventral mesencephalic (VM) dopaminergic neurons has been introduced in the clinic as an alternative treatment for PD (Lindvall et al, 1988(Lindvall et al, , 1992Madrazo et al, 1988;Freeman et al, 1995;Kordower et al, 1995;Borlongan et al, 1999;Borlongan, 2000). However, recent clinical trials have generated mixed results in that transplantation of fetal VM cells was shown to induce dyskinesia in some patients (Freed et al, 2001;Olanow et al, 2003), whereas excellent graft dopaminergic reinnervation of the parkinsonian affected striatum accompanied positive clinical improvements in transplanted patients who did not develop dyskinesia (Mendez et al, 2005).…”

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

“…Transplantation of stem cells into diseased nervous tissue (or by peripheral administration) could provide beneficial effects by introducing a reservoir of progenitor cells with the potential to distribute widely in the brain and differentiate into missing neuronal phenotypes, or by trophic factor support rescuing degenerating endogenous cells [8,10,11,17,31,33,41]. The cell transplantation approach has already been implemented as clinical trials for the treatment of Parkinson's disease [15,35,36] or stroke [1,27,34]. While the results of these studies were encouraging, it became clear that more basic research needs to be done before we can expect spectacular clinical results.…”

Cell Therapeutics in Parkinson's Disease

“…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].…”