Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease
Abstract
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.
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Clinical trials using neurotrophins in the treatment of Parkinson's disease are rather limited to GDNF administration instead of BDNF.
“Clinical trials using NTs in the treatment of PD are rather limited to GDNF administration instead of BDNF.”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [107]
Intraventricular infusions of growth factors typically fail to reach most neurons, and hence recent clinical trials used intraparenchymal infusions or gene delivery.
“Intraventricular infusions of growth factors typically fail to reach most neurons33, and hence recent clinical trials used intraparenchymal infusions or gene delivery34–37.”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [34]
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- Authors
- Gill, S. S., Patel, N. K., Hotton, G. R., O'Sullivan, K., McCarter, R., Bunnage, M., Brooks, D. J., Svendsen, C. N., & Heywood, P.
- Affiliations
- Frenchay Hospital (GB)
- Hammersmith Hospital (GB)
- University of Wisconsin–Madison (US)
- Corresponding author
- Gill, Steven S.
- Svendsen, Clive N.
- Venue
- Nature Medicine
- Published
- 2003-03-31
- Volume
- 9
- Issue
- 5
- Pages
- 589-595
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1996001296
- Cited by
- 1,290
- References
- 40
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 22 · 2023: 18 · 2022: 26 · 2021: 43 · 2020: 46 · 2019: 31 · 2018: 39 · 2017: 28 · 2016: 39 · 2015: 50 · 2014: 53 · 2013: 75 · 2012: 67
- FWCI
- 71.41
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-04-01)
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- glial cell line-derived neurotrophic factor, Parkinson's disease, putamen, neurotrophic factor delivery, dyskinesia, dopamine uptake, motor function, activities of daily living, neuroprotection
- MeSH terms
- Dihydroxyphenylalanine, Fluorine Radioisotopes, Humans, Middle Aged, Nerve Growth Factors, Parkinson Disease, Pilot Projects, Putamen, Research Design, Tomography, Emission-Computed, Glial Cell Line-Derived Neurotrophic Factor
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