ArticleHuman gene therapy2019
Virally Mediated Overexpression of Glial-Derived Neurotrophic Factor Elicits Age- and Dose-Dependent Neuronal Toxicity and Hearing Loss.
Article in Human gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Transduction Efficiency and Immunogenicity of Viral Vectors for Cochlear Gene Therapy: A Systematic Review of Preclinical Animal Studies.Frontiers in cellular neuroscience · 2021Pooled it
- Article
- A Review of the Clinical Applicability of Neurotrophins in Cochlear Implantation.Journal of audiology & otology · 2026Review
- Delivery of AAV vectors to the superior olivary complex enables efficient adult cochlear transduction via axonal transport.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors.Cell proliferation · 2025Article
- Concentration Dependent Effects of Human Cometin on Spiral Ganglion Neuron Survival and Neurite Outgrowth.Audiology & neuro-otology · 2025Article
- Semicircular canal drug delivery safely targets the inner ear perilymphatic space.JCI insight · 2024Article
- Advancements and future prospects of adeno-associated virus-mediated gene therapy for sensorineural hearing loss.Frontiers in neuroscience · 2024Review
- Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss.Biomedicines · 2023Review
- Current Advances in Adeno-Associated Virus-Mediated Gene Therapy to Prevent Acquired Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2022Review
- Improving Control of Gene Therapy-Based Neurotrophin Delivery for Inner Ear Applications.Frontiers in bioengineering and biotechnology · 2022Article
- The DNA methylation inhibitor RG108 protects against noise-induced hearing loss.Cell biology and toxicology · 2021Article
- Mechanism and Prevention of Spiral Ganglion Neuron Degeneration in the Cochlea.Frontiers in cellular neuroscience · 2021Review
- Cochlear Sox2Frontiers in cell and developmental biology · 2021Article
- A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and SynaptogenesisFrontiers in cellular neuroscience · 2021Article
- Advances in genome editing for genetic hearing loss.Advanced drug delivery reviews · 2021Review
- Neurotrophin gene therapy to promote survival of spiral ganglion neurons after deafness.Hearing research · 2020Review
- rAAV-Mediated Cochlear Gene Therapy: Prospects and Challenges for Clinical Application.Journal of clinical medicine · 2020Review
- Gene therapy for hearing loss.Human molecular genetics · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Contemporary cochlear implants (CI) are generally very effective for remediation of severe to profound sensorineural hearing loss, but outcomes are still highly variable. Auditory nerve survival is likely one of the major factors underlying this variability. Neurotrophin therapy therefore has been proposed for CI recipients, with the goal of improving outcomes by promoting improved survival of cochlear spiral ganglion neurons (SGN) and/or residual hair cells. Previous studies have shown that glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor, and neurotrophin-3 can rescue SGNs following insult. The current study was designed to determine whether adeno-associated virus vector serotype 5 (AAV-5) encoding either green fluorescent protein or GDNF can transduce cells in the mouse cochlea to express useful levels of neurotrophin and to approximate the optimum therapeutic dose(s) for transducing hair cells and SGN. The findings demonstrate that AAV-5 is a potentially useful gene therapy vector for the cochlea, resulting in extremely high levels of transgene expression in the cochlear inner hair cells and SGN. However, overexpression of human GDNF in newborn mice caused severe neurological symptoms and hearing loss, likely due to Purkinje cell loss and cochlear nucleus pathology. Thus, extremely high levels of transgene protein expression should be avoided, particularly for proteins that have neurological function in neonatal subjects.
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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.