Advanced

Gene therapy for Parkinson's disease : Disease modification by GDNF family of ligands

Kirik, Deniz LU ; Cederfjäll, Erik LU ; Halliday, Glenda and Petersén, LU (2017) In Neurobiology of Disease 97. p.179-188
Abstract

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor L-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so... (More)

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor L-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AAV, Adeno-associated virus, Dopamine, GDNF, Neurotrophic factors, Neurturin, Non-human primates, Viral vectors
in
Neurobiology of Disease
volume
97
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85002373824
ISSN
0969-9961
DOI
10.1016/j.nbd.2016.09.008
language
English
LU publication?
yes
id
b3851de9-b2a9-4434-99c0-498dc18247dc
date added to LUP
2017-03-20 14:43:36
date last changed
2017-06-20 03:00:07
@article{b3851de9-b2a9-4434-99c0-498dc18247dc,
  abstract     = {<p>Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor L-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease.</p>},
  author       = {Kirik, Deniz and Cederfjäll, Erik and Halliday, Glenda and Petersén, },
  issn         = {0969-9961},
  keyword      = {AAV,Adeno-associated virus,Dopamine,GDNF,Neurotrophic factors,Neurturin,Non-human primates,Viral vectors},
  language     = {eng},
  month        = {01},
  pages        = {179--188},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Gene therapy for Parkinson's disease : Disease modification by GDNF family of ligands},
  url          = {http://dx.doi.org/10.1016/j.nbd.2016.09.008},
  volume       = {97},
  year         = {2017},
}