ArticleMolecular therapy. Methods & clinical development2016
Viral-mediated Ntf3 overexpression disrupts innervation and hearing in nondeafened guinea pig cochleae.
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 19 papers.
What it found
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The trial behind it
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Biohybrid cochlear implants: neural interfaces, regenerative pathways, and translational benchmarks.Journal of neuroengineering and rehabilitation · 2026Review
- Optimizing Factors in Murine Whole-Organ Cochlea Culture.International journal of molecular sciences · 2025Article
- Cyclic AMP signaling promotes regeneration of cochlear synapses after excitotoxic or noise trauma.Frontiers in cellular neuroscience · 2024Article
- Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson's disease model.Frontiers in pharmacology · 2023Article
- Loss of the chromatin remodeler CHD7 impacts glial cells and myelination in the mouse cochlear spiral ganglion.Hearing research · 2022Article
- Improving Control of Gene Therapy-Based Neurotrophin Delivery for Inner Ear Applications.Frontiers in bioengineering and biotechnology · 2022Article
- Mechanism and Prevention of Spiral Ganglion Neuron Degeneration in the Cochlea.Frontiers in cellular neuroscience · 2021Review
- Advances in genome editing for genetic hearing loss.Advanced drug delivery reviews · 2021Review
- How electrically evoked compound action potentials in chronically implanted guinea pigs relate to auditory nerve health and electrode impedance.The Journal of the Acoustical Society of America · 2020Article
- Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Effects of Neurotrophin-3 on Intrinsic Neuronal Properties at a Central Auditory Structure.Neuroscience insights · 2020Article
- Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3.Scientific reports · 2019Article
- Cochlear Gene Therapy.Cold Spring Harbor perspectives in medicine · 2019Review
- Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level cis-eQTL.PLoS genetics · 2019Article
- Translating animal models to human therapeutics in noise-induced and age-related hearing loss.Hearing research · 2019Review
- Photobiomodulation promotes adenoviral gene transduction in auditory cells.Lasers in medical science · 2019Article
- Gene Therapy for Human Sensorineural Hearing Loss.Frontiers in cellular neuroscience · 2019Review
- Genetic Hearing Loss and Gene Therapy.Genomics & informatics · 2018Article
- Potential of Gene and Cell Therapy for Inner Ear Hair Cells.BioMed research international · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Synaptopathy in the cochlea occurs when the connection between inner hair cells and the auditory nerve is disrupted, leading to impaired hearing and nerve degeneration. Experiments using transgenic mice have shown that overexpression of NT3 by supporting cells repairs synaptopathy caused by overstimulation. To accomplish such therapy in the clinical setting, it would be necessary to activate the neurotrophin receptor on auditory neurons by other means. Here we test the outcome of NT3 overexpression using viral-mediated gene transfer into the perilymph versus the endolymph of the normal guinea pig cochlea. We inoculated two different Ntf3 viral vectors, adenovirus (Adv) or adeno-associated virus (AAV) into the perilymph, to facilitate transgene expression in the mesothelial cells and cochlear duct epithelium, respectively. We assessed outcomes by comparing Auditory brainstem response (ABR) thresholds prior to that at baseline to thresholds at 1 and 3 weeks after inoculation, and then performed histologic evaluation of hair cells, nerve endings, and synaptic ribbons. We observed hearing threshold shifts as well as disorganization of peripheral nerve endings and disruption of synaptic connections between inner hair cells and peripheral nerve endings with both vectors. The data suggest that elevation of NT3 levels in the cochlear fluids can disrupt innervation and degrade hearing.
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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.