ArticleMolecular therapy. Methods & clinical development2016
A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.Molecular therapy. Methods & clinical development · 2023Article
- Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons.Molecular brain · 2023Article
- Tetracycline-Inducible and Reversible Stable Gene Expression in Human iPSC-Derived Neural Progenitors and in the Postnatal Mouse Brain.Current protocols · 2023Article
- A Dual-Function "TRE-Lox" System for Genetic Deletion or Reversible, Titratable, and Near-Complete Downregulation of Cathepsin D.International journal of molecular sciences · 2023Article
- 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
- Challenges of repurposing tetracyclines for the treatment of Alzheimer's and Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Neurotrophins as Therapeutic Agents for Parkinson's Disease; New Chances From Focused Ultrasound?Frontiers in neuroscience · 2022Review
- Mouse Embryonic Stem Cells Expressing GDNF Show Enhanced Dopaminergic Differentiation and Promote Behavioral Recovery After Grafting in Parkinsonian Rats.Frontiers in cell and developmental biology · 2021Article
- Improving therapeutic potential of GDNF family ligands.Cell and tissue research · 2020Review
- GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease.Journal of clinical medicine · 2020Review
- In-Depth Characterization of a Mifepristone-Regulated Expression System for AAV5-Mediated Gene Therapy in the Liver.Molecular therapy. Methods & clinical development · 2019Article
- Destabilizing Domains Enable Long-Term and Inert Regulation of GDNF Expression in the Brain.Molecular therapy. Methods & clinical development · 2018Article
- Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury.Brain : a journal of neurology · 2018Article
- AAVvector-mediated in vivo reprogramming into pluripotency.Nature communications · 2018Article
- Inducible Expression of GDNF in Transplanted iPSC-Derived Neural Progenitor Cells.Stem cell reports · 2018Article
- Doxycycline Used for Control of Transgene Expression has its Own Effects on Behaviors and Bcl-xL in the Rat Hippocampus.Cellular and molecular neurobiology · 2018Article
- Tetracycline-Inducible and Reversible Stable Gene Expression in Human iPSC-Derived Neural Progenitors and in the Postnatal Mouse Brain.Current protocols in stem cell biology · 2017Article
- Review
- Glial Cell Line-Derived Neurotrophic Factor Gene Delivery in Parkinson's Disease: A Delicate Balance between Neuroprotection, Trophic Effects, and Unwanted Compensatory Mechanisms.Frontiers in neuroanatomy · 2017Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF) intracerebral administration to treat PD. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a clinically-approved dose, reaches the brain in sufficient amounts to induce a therapeutic effect. We describe a highly-sensitive doxycycline-inducible adeno-associated virus (AAV) vector. This vector allowed for the first time a longitudinal analysis of inducible transgene expression in the brain using bioluminescence imaging. To evaluate the dose range of GDNF biological activity, the inducible AAV vector (8.0 × 10(9) viral genomes) was injected in the rat striatum at four delivery sites and increasing doxycycline doses administered orally. ERK/Akt signaling activation as well as tyrosine hydroxylase downregulation, a consequence of long-term GDNF treatment, were induced at plasmatic doxycycline concentrations of 140 and 320 ng/ml respectively, which are known not to increase antibiotic-resistant microorganisms in patients. In these conditions, GDNF covered the majority of the striatum. No behavioral abnormalities or weight loss were observed. Motor asymmetry resulting from unilateral GDNF treatment only appeared with a 2.5-fold higher vector and a 13-fold higher inducer doses. Our data suggest that using the herein-described inducible AAV vector, biological effects of GDNF can be obtained in response to sub-antimicrobial doxycycline doses.
Identifiers
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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.