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Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Widner, H LU ; Tetrud, J; Rehncrona, S LU ; Snow, B J; Brundin, Patrik LU ; Gustavii, Björn LU ; Björklund, A LU ; Lindvall, O LU and Langston, J W (1992) In New England Journal of Medicine 327(22). p.63-1556
Abstract

BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.

METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic... (More)

BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.

METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation.

RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications.

CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.

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keywords
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Adult, Caudate Nucleus, Corpus Striatum, Dihydroxyphenylalanine, Dopamine, Female, Fetal Tissue Transplantation, Humans, Immunosuppression, Levodopa, Male, Mesencephalon, Motor Activity, Parkinson Disease, Secondary, Putamen, Stereotaxic Techniques, Time Factors, Tomography, Emission-Computed, Case Reports, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
in
New England Journal of Medicine
volume
327
issue
22
pages
8 pages
publisher
Massachusetts Medical Society
external identifiers
  • scopus:0026458624
ISSN
0028-4793
DOI
language
English
LU publication?
yes
id
9d256e8c-a9bb-4d3e-b7c8-712b4775727d
date added to LUP
2017-04-19 18:30:56
date last changed
2018-06-10 05:18:04
@article{9d256e8c-a9bb-4d3e-b7c8-712b4775727d,
  abstract     = {<p>BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.</p><p>METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation.</p><p>RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications.</p><p>CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.</p>},
  author       = {Widner, H and Tetrud, J and Rehncrona, S and Snow, B J and Brundin, Patrik and Gustavii, Björn and Björklund, A and Lindvall, O and Langston, J W},
  issn         = {0028-4793},
  keyword      = {1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine,Adult,Caudate Nucleus,Corpus Striatum,Dihydroxyphenylalanine,Dopamine,Female,Fetal Tissue Transplantation,Humans,Immunosuppression,Levodopa,Male,Mesencephalon,Motor Activity,Parkinson Disease, Secondary,Putamen,Stereotaxic Techniques,Time Factors,Tomography, Emission-Computed,Case Reports,Clinical Trial,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {63--1556},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)},
  url          = {http://dx.doi.org/},
  volume       = {327},
  year         = {1992},
}