Cited by 955Parkinson's Disease Mechanisms and TreatmentsNerve injury and regenerationNuclear Receptors and Signaling

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Functional recovery in parkinsonian monkeys treated with GDNF

Gash, Don M., Zhang, Zhiming, Ovadia, Aliza, Cass, Wayne A., Yi, Ai, Simmerman, Linda, Russell, Deborah, Martin, David, Lapchak, Paul A., Collins, Frank, Hoffer, Barry J., Gerhard, Greg A.·1996·Nature

DOI 10.1038/380252a0

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Abstract

Parkinson's disease results from the progressive degeneration of dopamine neurons that innervate the striatum. In rodents, glial-cell-line-derived neurotrophic factor (GDNF) stimulates an increase in midbrain dopamine levels, protects dopamine neurons from some neurotoxins, and maintains injured dopamine neurons. Here we extend the rodent studies to an animal closer to the human in brain organization and function, by evaluating the effects of GDNF injected intracerebrally in rhesus monkeys that have had the symptomatology and pathophysiological features of Parkinson's disease induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The recipients of GDNF displayed significant improvements in three of the cardinal symptoms of parkinsonism: bradykinesia, rigidity and postural instability. GDNF administered every four weeks maintained functional recovery. On the lesioned side of GDNF-treated animals, dopamine levels in the midbrain and globus pallidus were twice as high, and nigral dopamine neurons were, on average, 20% larger, with an increased fibre density. The results indicate that GDNF may be of benefit in the treatment of Parkinson's disease.

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Authors: Gash, D. M., Zhang, Z., Ovadia, A., Cass, W. A., Yi, A., Simmerman, L., Russell, D., Martin, D., Lapchak, P. A., Collins, F., Hoffer, B. J., & Gerhard, G. A.
Affiliations: University of Kentucky (US)
ORCID: Gash, Don M.
Zhang, Zhiming
Cass, Wayne A.
Lapchak, Paul A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1996-03
Volume: 380
Issue: 6571
Pages: 252-255
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/380252a0
OpenAlex: W1971258758
Cited by: 955
References: 22
Citations by year: 2026: 2 · 2025: 12 · 2024: 10 · 2023: 9 · 2022: 20 · 2021: 16 · 2020: 23 · 2019: 18 · 2018: 20 · 2017: 13 · 2016: 21 · 2015: 27 · 2014: 24 · 2013: 30 · 2012: 27
FWCI: 51.18
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: Parkinson's disease, glial cell line-derived neurotrophic factor, MPTP-induced parkinsonism, rhesus monkeys, dopaminergic neurons, midbrain dopamine, globus pallidus, nigral neurons, bradykinesia, rigidity, postural instability, functional recovery, neuroprotection, neurotrophic therapy
MeSH terms: Animals, Dopamine, Female, Humans, Macaca mulatta, Mesencephalon, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Parkinson Disease, Recombinant Proteins, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Glial Cell Line-Derived Neurotrophic Factor

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Functional recovery in parkinsonian monkeys treated with GDNF

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