ArticleGene therapy2019
GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration.
Article in Gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Molecular Determinants of A9 Dopaminergic Neurons.Neuromolecular medicine · 2025Review
- Neurotrophic factors for Parkinson's disease: Current status, progress, and remaining questions. Conclusions from a 2023 workshop.Journal of Parkinson's disease · 2024Review
- Cinnamaldehyde Attenuates the Expression of IBA1 and GFAP to Inhibit Glial Cell Activation and Inflammation in the MPTP-Induced Acute Parkinson's Disease Model.Parkinson's disease · 2024Article
- Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport.Frontiers in aging neuroscience · 2023Review
- Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic.Neural regeneration research · 2022Review
- Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.Glycoconjugate journal · 2022Review
- The Effects of the Task Balance Training Program on the Glial Cell Line-Derived Neurotrophic Factor Levels, Cognitive Function, and Postural Balance in Old People.BioMed research international · 2022Article
- Mechanistic Insight from Preclinical Models of Parkinson's Disease Could Help Redirect Clinical Trial Efforts in GDNF Therapy.International journal of molecular sciences · 2021Review
- Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson's Disease. A Systematic Review.Frontiers in aging neuroscience · 2021Article
- Neurotrophin gene therapy to promote survival of spiral ganglion neurons after deafness.Hearing research · 2020Review
- Cellular Localization ofBrain sciences · 2020Article
- Review
- Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System.International journal of molecular sciences · 2020Review
- Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease.Brain pathology (Zurich, Switzerland) · 2019Article
- An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function.Journal of Parkinson's diseaseReview
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glial cell-line derived neurotrophic factor (GDNF) is a promising therapeutic molecule to treat Parkinson's disease. Despite an excellent profile in experimental settings, clinical trials testing GDNF have failed. One of the theories to explain these negative outcomes is that the clinical trials were done in late-stage patients that have advanced nigrostriatal degeneration and may therefore not respond to a neurotrophic factor therapy. Based on this idea, we tested if the stage of nigrostriatal degeneration is important for GDNF-based therapies. Lentiviral vectors expressing regulated GDNF were delivered to the striatum of rats to allow GDNF expression to be turned on either while the nigrostriatal system was degenerating or after the nigrostriatal system had been fully lesioned by 6-OHDA. In the group of animals where GDNF expression was on during degeneration, neurons were rescued and there was a reversal of motor deficits. Turning GDNF expression on after the nigrostriatal system was lesioned did not rescue neurons or reverse motor deficits. In fact, these animals were indistinguishable from the control groups. Our results suggest that GDNF can reverse motor deficits and nigrostriatal pathology despite an ongoing nigrostriatal degeneration, if there is still a sufficient number of remaining neurons to respond to therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.