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GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop

Barker, Roger A. LU ; Björklund, Anders LU ; Gash, Don M. ; Whone, Alan ; Van Laar, Amber ; Kordower, Jeffrey H. ; Bankiewicz, Krystof ; Kieburtz, Karl ; Saarma, Mart and Booms, Sigrid , et al. (2020) In Journal of Parkinson's Disease 10(3). p.875-891
Abstract

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the... (More)

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
clinical trials, dopaminergic neurons, GDNF, NRTN, Parkinson's disease
in
Journal of Parkinson's Disease
volume
10
issue
3
pages
17 pages
publisher
IOS Press
external identifiers
  • pmid:32508331
  • scopus:85089128922
ISSN
1877-7171
DOI
10.3233/JPD-202004
language
English
LU publication?
yes
id
3812f157-7c5c-4cab-afd4-18cff77f3f03
date added to LUP
2020-08-20 09:54:12
date last changed
2020-10-20 02:55:12
@article{3812f157-7c5c-4cab-afd4-18cff77f3f03,
  abstract     = {<p>The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.</p>},
  author       = {Barker, Roger A. and Björklund, Anders and Gash, Don M. and Whone, Alan and Van Laar, Amber and Kordower, Jeffrey H. and Bankiewicz, Krystof and Kieburtz, Karl and Saarma, Mart and Booms, Sigrid and Huttunen, Henri J. and Kells, Adrian P. and Fiandaca, Massimo S. and Stoessl, A. Jon and Eidelberg, David and Federoff, Howard and Voutilainen, Merja H. and Dexter, David T. and Eberling, Jamie and Brundin, Patrik and Isaacs, Lyndsey and Mursaleen, Leah and Bresolin, Eros and Carroll, Camille and Coles, Alasdair and Fiske, Brian and Matthews, Helen and Lungu, Codrin and Wyse, Richard K. and Stott, Simon and Lang, Anthony E.},
  issn         = {1877-7171},
  language     = {eng},
  number       = {3},
  pages        = {875--891},
  publisher    = {IOS Press},
  series       = {Journal of Parkinson's Disease},
  title        = {GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop},
  url          = {http://dx.doi.org/10.3233/JPD-202004},
  doi          = {10.3233/JPD-202004},
  volume       = {10},
  year         = {2020},
}