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Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease

Lindvall, O LU ; Sawle, Guy; Widner, H LU ; Rothwell, J C; Björklund, A LU ; Brooks, D E; Brundin, P LU ; Frackowiak, R S; Marsden, C D and Odin, P LU (1994) In Annals of Neurology 35(2). p.80-172
Abstract

Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1... (More)

Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.

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organization
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published
subject
keywords
Brain Tissue Transplantation, Dihydroxyphenylalanine, Dopamine, Fetal Tissue Transplantation, Humans, Levodopa, Mesencephalon, Parkinson Disease, Putamen, Journal Article, Research Support, Non-U.S. Gov't
in
Annals of Neurology
volume
35
issue
2
pages
80 - 172
publisher
John Wiley and Sons Inc.
external identifiers
  • scopus:0027977759
ISSN
0364-5134
DOI
10.1002/ana.410350208
language
English
LU publication?
yes
id
dcabc7d4-59e7-48e7-87aa-2e0c934df34d
date added to LUP
2017-04-19 18:28:07
date last changed
2017-09-24 05:09:51
@article{dcabc7d4-59e7-48e7-87aa-2e0c934df34d,
  abstract     = {<p>Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.</p>},
  author       = {Lindvall, O and Sawle, Guy and Widner, H and Rothwell, J C and Björklund, A and Brooks, D E and Brundin, P and Frackowiak, R S and Marsden, C D and Odin, P},
  issn         = {0364-5134},
  keyword      = {Brain Tissue Transplantation,Dihydroxyphenylalanine,Dopamine,Fetal Tissue Transplantation,Humans,Levodopa,Mesencephalon,Parkinson Disease,Putamen,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {80--172},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Annals of Neurology},
  title        = {Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease},
  url          = {http://dx.doi.org/10.1002/ana.410350208},
  volume       = {35},
  year         = {1994},
}