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Cell therapy for Parkinson's disease: Why it doesn't work every time
The clinical experience with cell replacement therapy for advanced PD has yielded notable successes and failures. A recent autopsy case report of an individual that received implants of fetal dopamine neurons 16 years previously, but at no time experienced clinical benefit despite the best documente...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771700/ https://www.ncbi.nlm.nih.gov/pubmed/31234239 http://dx.doi.org/10.1002/mds.27742 |
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author | Collier, Timothy J. Sortwell, Caryl E. Mercado, Natosha M. Steece‐Collier, Kathy |
author_facet | Collier, Timothy J. Sortwell, Caryl E. Mercado, Natosha M. Steece‐Collier, Kathy |
author_sort | Collier, Timothy J. |
collection | PubMed |
description | The clinical experience with cell replacement therapy for advanced PD has yielded notable successes and failures. A recent autopsy case report of an individual that received implants of fetal dopamine neurons 16 years previously, but at no time experienced clinical benefit despite the best documented survival of grafted neurons and most extensive reinnervation of the striatum, raises sobering issues. With good reason, a great deal of effort in cell replacement science continues to focus on optimizing the cell source and implantation procedure. Here, we describe our preclinical studies in aged rats indicating that despite survival of large numbers of transplanted dopamine neurons and dense reinnervation of the striatum, synaptic connections between graft and host are markedly decreased and behavioral recovery is impaired. This leads us to the hypothesis that the variability in therapeutic response to dopamine neuron grafts may be less about the viability of transplanted neurons and more about the integrity of the aged, dopamine‐depleted striatum and its capacity for repair. Replacement of dopamine innervation only can be fully effective if the correct target is present. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. |
format | Online Article Text |
id | pubmed-6771700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67717002019-10-07 Cell therapy for Parkinson's disease: Why it doesn't work every time Collier, Timothy J. Sortwell, Caryl E. Mercado, Natosha M. Steece‐Collier, Kathy Mov Disord Gaps & Controversies The clinical experience with cell replacement therapy for advanced PD has yielded notable successes and failures. A recent autopsy case report of an individual that received implants of fetal dopamine neurons 16 years previously, but at no time experienced clinical benefit despite the best documented survival of grafted neurons and most extensive reinnervation of the striatum, raises sobering issues. With good reason, a great deal of effort in cell replacement science continues to focus on optimizing the cell source and implantation procedure. Here, we describe our preclinical studies in aged rats indicating that despite survival of large numbers of transplanted dopamine neurons and dense reinnervation of the striatum, synaptic connections between graft and host are markedly decreased and behavioral recovery is impaired. This leads us to the hypothesis that the variability in therapeutic response to dopamine neuron grafts may be less about the viability of transplanted neurons and more about the integrity of the aged, dopamine‐depleted striatum and its capacity for repair. Replacement of dopamine innervation only can be fully effective if the correct target is present. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. John Wiley & Sons, Inc. 2019-06-24 2019-08 /pmc/articles/PMC6771700/ /pubmed/31234239 http://dx.doi.org/10.1002/mds.27742 Text en © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Gaps & Controversies Collier, Timothy J. Sortwell, Caryl E. Mercado, Natosha M. Steece‐Collier, Kathy Cell therapy for Parkinson's disease: Why it doesn't work every time |
title | Cell therapy for Parkinson's disease: Why it doesn't work every time |
title_full | Cell therapy for Parkinson's disease: Why it doesn't work every time |
title_fullStr | Cell therapy for Parkinson's disease: Why it doesn't work every time |
title_full_unstemmed | Cell therapy for Parkinson's disease: Why it doesn't work every time |
title_short | Cell therapy for Parkinson's disease: Why it doesn't work every time |
title_sort | cell therapy for parkinson's disease: why it doesn't work every time |
topic | Gaps & Controversies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771700/ https://www.ncbi.nlm.nih.gov/pubmed/31234239 http://dx.doi.org/10.1002/mds.27742 |
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