Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain
Cederfjäll, Erik LU ; Sahin, Gurdal LU
and Kirik, Deniz
LU
(2012)
In Neurobiology of Disease
48(2).
p.222-227
- Abstract
- L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of L-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term.... (More)
- L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of L-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease. (C) 2011 Published by Elsevier Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3146761
- author
- Cederfjäll, Erik
LU
; Sahin, Gurdal
LU
and Kirik, Deniz
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adeno-associated viral vector, Aromatic L-amino acid decarboxylase, L-DOPA, Parkinson's disease, Tyrosine hydroxylase
- in
- Neurobiology of Disease
- volume
- 48
- issue
- 2
- pages
- 222 - 227
- publisher
- Elsevier
- external identifiers
-
- wos:000307911400007
- scopus:84865551695
- pmid:22048069
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2011.10.017
- language
- English
- LU publication?
- yes
- id
- a100ade7-6412-412d-9984-4a4cf114592f (old id 3146761)
- date added to LUP
- 2016-04-01 09:49:11
- date last changed
- 2022-05-13 01:55:18
@article{a100ade7-6412-412d-9984-4a4cf114592f,
abstract = {{L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of L-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease. (C) 2011 Published by Elsevier Inc.}},
author = {{Cederfjäll, Erik and Sahin, Gurdal and Kirik, Deniz}},
issn = {{0969-9961}},
keywords = {{Adeno-associated viral vector; Aromatic L-amino acid decarboxylase; L-DOPA; Parkinson's disease; Tyrosine hydroxylase}},
language = {{eng}},
number = {{2}},
pages = {{222--227}},
publisher = {{Elsevier}},
series = {{Neurobiology of Disease}},
title = {{Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain}},
url = {{http://dx.doi.org/10.1016/j.nbd.2011.10.017}},
doi = {{10.1016/j.nbd.2011.10.017}},
volume = {{48}},
year = {{2012}},
}