ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Tight Long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients.Neurology · 2013Trial
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.Gene therapy · 2024Article
- Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.Molecular therapy. Methods & clinical development · 2023Article
- EpiPro, a Novel, Synthetic, Activity-Regulated Promoter That Targets Hyperactive Neurons in Epilepsy for Gene Therapy Applications.International journal of molecular sciences · 2023Article
- Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons.International journal of molecular sciences · 2023Article
- Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Regulated hAAT Expression from a Novel rAAV Vector and Its Application in the Prevention of Type 1 Diabetes.Journal of clinical medicine · 2019Article
- Modulated expression of the HIV-1 2LTR zinc finger efficiently interferes with the HIV integration process.Bioscience reports · 2018Article
- Development of an inducible anti-VEGF rAAV gene therapy strategy for the treatment of wet AMD.Scientific reports · 2018Article
- Silencing Alpha Synuclein in Mature Nigral Neurons Results in Rapid Neuroinflammation and Subsequent Toxicity.Frontiers in molecular neuroscience · 2018Article
- Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.Molecular therapy. Nucleic acids · 2017Article
- Article
- Flexible, AAV-equipped Genetic Modules for Inducible Control of Gene Expression in Mammalian Brain.Molecular therapy. Nucleic acids · 2016Article
- Gene Therapy Models of Alzheimer's Disease and Other Dementias.Methods in molecular biology (Clifton, N.J.) · 2016Article
- A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses.Molecular therapy. Methods & clinical development · 2016Article
- Tet-On Systems For Doxycycline-inducible Gene Expression.Current gene therapy · 2016Review
- Controlled Striatal DOPA Production From a Gene Delivery System in a Rodent Model of Parkinson's Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.British journal of clinical pharmacology · 2013Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Glial cell line-derived neurotrophic factor (GDNF) gene transfer is being developed as a treatment for Parkinson's disease (PD). Due to the potential for side effects, external transgene regulation should enhance this strategy's safety profile. Here, we demonstrate dynamic control during long-term expression of GDNF using a recombinant adeno-associated virus (rAAV)-based bicistronic tetracycline (tet)-off construct. Nigrostriatal GDNF overexpression induces body weight alterations in rodents, enabling longitudinal in vivo tracking of GDNF expression after nigral vector delivery. Regulated GDNF expression was highly sensitive to dietary doxycycline (DOX), displaying undetectable striatal GDNF levels at serum DOX levels below those required for antimicrobial activity. However, in the absence of DOX, striatal GDNF levels exceeded levels required for efficacy in PD models. We also demonstrate the absence of a series of known GDNF-associated side effects when using direct intrastriatal vector delivery. Therefore, this single rAAV vector system meets most of the requirements for an experimental reagent for treatment of PD.
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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.