ArticleStereotactic and functional neurosurgery2014
Titer and product affect the distribution of gene expression after intraputaminal convection-enhanced delivery.
Article in Stereotactic and functional neurosurgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates.Current research in neurobiology · 2023Article
- Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors.Frontiers in bioengineering and biotechnology · 2023Article
- Article
- Recent developments in nucleic acid-based therapies for Parkinson's disease: Current status, clinical potential, and future strategies.Frontiers in pharmacology · 2022Review
- Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Transduction patterns in the CNS following various routes of AAV-5-mediated gene delivery.Gene therapy · 2021Article
- PhP.B Enhanced Adeno-Associated Virus Mediated-Expression Following Systemic Delivery or Direct Brain Administration.Frontiers in bioengineering and biotechnology · 2021Article
- Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain.Molecular therapy. Methods & clinical development · 2020Article
- The role of nonhuman primate models in the development of cell-based therapies for Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Gene Therapy for Parkinson's Disease, An Update.Journal of Parkinson's disease · 2018Review
- Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data.International journal of molecular sciences · 2017Review
- Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons.Cell transplantation · 2017Article
- MR-guided parenchymal delivery of adeno-associated viral vector serotype 5 in non-human primate brain.Gene therapy · 2017Article
- Overexpressing Corticotropin-Releasing Factor in the Primate Amygdala Increases Anxious Temperament and Alters Its Neural Circuit.Biological psychiatry · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundThe efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression.
objectivesTo assess whether the distribution of gene expression is affected by vector titer and protein type.
methodsFour adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. The inoculations were conducted using convection-enhanced delivery and intraoperative MRI (IMRI).
resultsIMRI confirmed targeting and infusion cloud irradiation from the catheter tip into the surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and GDNF expression ipsilateral to the injection site that had a titer-dependent distribution. GFP and GDNF expression was also observed in fibers in the substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport. Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by direct retrograde transport of the vector. GDNF was present in many neurons of the SNpc and SNpr.
conclusionsAfter controlling for target and infusate volume, the intracerebral distribution of the gene product was affected by the vector titer and product biology.
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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.