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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Barker, Roger A 
Björklund, Anders 
Gash, Don M 
Whone, Alan 
Van Laar, Amber 

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 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.

Description

Keywords

GDNF, NRTN, Parkinson’s disease, clinical trials, dopaminergic neurons, Animals, Dopaminergic Neurons, Genetic Therapy, Glial Cell Line-Derived Neurotrophic Factor, Humans, Neuroprotective Agents, Parkinson Disease

Journal Title

J Parkinsons Dis

Conference Name

Journal ISSN

1877-7171
1877-718X

Volume Title

10

Publisher

IOS Press

Rights

All rights reserved