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Understanding and Prevention of “Therapy-” Induced Dyskinesias

L-dopa is the most effective, currently available treatment for Parkinson's disease (PD), but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID) in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of m...

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Autores principales: Aviles-Olmos, Iciar, Kefalopoulou, Zinovia, Foltynie, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366244/
https://www.ncbi.nlm.nih.gov/pubmed/22685687
http://dx.doi.org/10.1155/2012/640815
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author Aviles-Olmos, Iciar
Kefalopoulou, Zinovia
Foltynie, Thomas
author_facet Aviles-Olmos, Iciar
Kefalopoulou, Zinovia
Foltynie, Thomas
author_sort Aviles-Olmos, Iciar
collection PubMed
description L-dopa is the most effective, currently available treatment for Parkinson's disease (PD), but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID) in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of multiple ongoing studies as potential ways of relieving symptoms of PD without the complication of dyskinesia. However, the spectre of dyskinesia in the absence of L-dopa, the so-called “off-phase” or graft-induced dyskinesia (GID), remains a major obstacle particularly in the further development of cell therapy in PD, but it is also a concern for proponents of gene therapy approaches. LID results from nonphysiological dopamine release, supersensitivity of dopamine receptors, and consequent abnormal signalling through mechanisms of synaptic plasticity. Restoration of physiological circuitry within the basal ganglia loops is ultimately the aim of all cell and gene therapy approaches but each using distinctive strategies and accompanied by risks of exacerbation of LID or development of “off-phase”/GID. In this paper we discuss the details of what is understood regarding the development of dyskinesias with relevance to cell and gene therapy and potential strategies to minimize their occurrence.
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spelling pubmed-33662442012-06-08 Understanding and Prevention of “Therapy-” Induced Dyskinesias Aviles-Olmos, Iciar Kefalopoulou, Zinovia Foltynie, Thomas Parkinsons Dis Review Article L-dopa is the most effective, currently available treatment for Parkinson's disease (PD), but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID) in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of multiple ongoing studies as potential ways of relieving symptoms of PD without the complication of dyskinesia. However, the spectre of dyskinesia in the absence of L-dopa, the so-called “off-phase” or graft-induced dyskinesia (GID), remains a major obstacle particularly in the further development of cell therapy in PD, but it is also a concern for proponents of gene therapy approaches. LID results from nonphysiological dopamine release, supersensitivity of dopamine receptors, and consequent abnormal signalling through mechanisms of synaptic plasticity. Restoration of physiological circuitry within the basal ganglia loops is ultimately the aim of all cell and gene therapy approaches but each using distinctive strategies and accompanied by risks of exacerbation of LID or development of “off-phase”/GID. In this paper we discuss the details of what is understood regarding the development of dyskinesias with relevance to cell and gene therapy and potential strategies to minimize their occurrence. Hindawi Publishing Corporation 2012 2012-05-23 /pmc/articles/PMC3366244/ /pubmed/22685687 http://dx.doi.org/10.1155/2012/640815 Text en Copyright © 2012 Iciar Aviles-Olmos et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Aviles-Olmos, Iciar
Kefalopoulou, Zinovia
Foltynie, Thomas
Understanding and Prevention of “Therapy-” Induced Dyskinesias
title Understanding and Prevention of “Therapy-” Induced Dyskinesias
title_full Understanding and Prevention of “Therapy-” Induced Dyskinesias
title_fullStr Understanding and Prevention of “Therapy-” Induced Dyskinesias
title_full_unstemmed Understanding and Prevention of “Therapy-” Induced Dyskinesias
title_short Understanding and Prevention of “Therapy-” Induced Dyskinesias
title_sort understanding and prevention of “therapy-” induced dyskinesias
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366244/
https://www.ncbi.nlm.nih.gov/pubmed/22685687
http://dx.doi.org/10.1155/2012/640815
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