ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Efficient gene therapy for Parkinson's disease using astrocytes as hosts for localized neurotrophic factor delivery.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- Dual-Pathway Astrocyte Failure in Parkinson's Disease: Therapeutic Targeting of Nrf2/TFEB Suppression and cGAS-STING/Ferroptosis Activation.Molecular neurobiology · 2026Review
- Review
- Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.Fundamental research · 2024Article
- In vivo imaging of astrocytes in the whole brain with engineered AAVs and diffusion-weighted magnetic resonance imaging.Molecular psychiatry · 2024Article
- Human serum-derived α-synuclein auto-antibodies mediate NMDA receptor-dependent degeneration of CNS neurons.Journal of neuroinflammation · 2024Article
- 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
- Astrocyte-specific deletion of the transcription factor Yin Yang 1 in murine substantia nigra mitigates manganese-induced dopaminergic neurotoxicity.The Journal of biological chemistry · 2020Article
- Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease.Redox biology · 2020Review
- Improved tools to study astrocytes.Nature reviews. Neuroscience · 2020Review
- GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease.Journal of clinical medicine · 2020Review
- Protective Functions of Reactive Astrocytes Following Central Nervous System Insult.Frontiers in immunology · 2020Review
- Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson's Disease Animal Models from a Molecular Signaling Perspective.Neural plasticity · 2020Review
- Challenges of gene delivery to the central nervous system and the growing use of biomaterial vectors.Brain research bulletin · 2019Review
- Astrocyte-selective AAV gene therapy through the endogenous GFAP promoter results in robust transduction in the rat spinal cord following injury.Gene therapy · 2019Article
- Neuroprotective Effect of Echinacoside in Subacute Mouse Model of Parkinson's Disease.BioMed research international · 2019Article
- A MicroRNA124 Target Sequence Restores Astrocyte Specificity of gfaABCMolecular therapy. Nucleic acids · 2017Article
- Lentiviral Delivery of miR-133b Improves Functional Recovery After Spinal Cord Injury in Mice.Molecular neurobiology · 2017Article
- Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model.Nano letters · 2017Article
- Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect.Ageing research reviews · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current gene therapy approaches for Parkinson's disease (PD) deliver neurotrophic factors like glial cell line-derived neurotrophic factor (GDNF) or neurturin via neuronal transgene expression. Since these potent signaling-inducing neurotrophic factors can be distributed through long-distance neuronal projections to unaffected brain sites, this mode of delivery may eventually cause side effects. To explore a localized and thus potentially safer alternative for gene therapy of PD, we expressed GDNF exclusively in astrocytes and evaluated the efficacy of this approach in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rat 6-hydroxy-dopamine (6-OHDA) models of PD. In terms of protection of dopaminergic cell bodies and projections, dopamine (DA) synthesis and behaviour, astrocyte-derived GDNF demonstrated the same efficacy as neuron-derived GDNF. In terms of safety, unilateral striatal GDNF expression in astrocytes did not result in delivery of bio-active GDNF to the contralateral hemispheres (potential off-target sites) as happened when GDNF was expressed in neurons. Thus, astrocytic GDNF expression represents a localized but efficient alternative to current gene therapeutic strategies for the treatment of PD, especially if viral vectors with enhanced tissue penetration are considered. Astrocytic neurotrophic factor expression may open new venues for neurotrophic factor-based gene therapy targeting severe diseases of the brain.
Indexed as
Identifiers
What OpenQuestion holds
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.