Submit to Biomolecules Review for Biomolecules Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Inner Ear Therapeutics

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 39224

Share This Special Issue

Special Issue Editors

Dr. Erik de Vrieze

E-Mail Website
Guest Editor

Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Interests: inherited deafness; usher syndrome; antisense oligonucleotides; genetic therapy; zebrafish models

Dr. Jennifer J. Lentz

E-Mail Website
Guest Editor

Department of Otorhinolaryngology & Biocommunications, Neuroscience Center of Excellence, 2020 Gravier Street, LSU Health-New Orleans, New Orleans, LA 70112, USA
Interests: usher syndrome; hereditary deafness; retinitis pigmentosa; sensory cell biology; antisense oligonucleotides; gene therapy; mouse models

Dr. Erwin Van Wijk

E-Mail Website
Guest Editor

Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Interests: usher syndrome; retinitis pigmentosa; antisense oligonucleotides; inherited deafness; genetic therapy; zebrafish models

Special Issue Information

Dear Colleagues,

The World Health Organization (WHO) estimates that ~5% of the world’s population suffers from “disabling” inner ear diseases that affect hearing and balance. As such, the development of eﬀective and safe treatments for auditory and vestibular disorders has become increasingly important. Drug development is challenging and must overcome many obstacles. A fundamental hurdle is the ability to translate positive results obtained in animal models to humans. Proof-of-principle studies of genetic therapies show great promise as novel treatments for auditory and vestibular loss. However, there is also an urgent need for novel treatments for acquired forms of deafness and imbalance caused by age, noise, blast, and ototoxic drugs. Identifying potential participants and robust outcome measures for conducting clinical trials is also an obstacle to developing drugs that requires clinical collaboration to overcome.

In this Special Issue, entitled Inner Ear Therapeutics, we aim to provide a platform for all aspects of therapeutic research into loss of hearing and balance. We would like to invite scientists to submit manuscripts that focus on the design and preclinical validation of novel treatments, the optimization of delivery methods for inner ear drugs, and the identification of outcome measures to determine therapeutic efficacy. Contributions to this Special Issue are invited in the format of original research papers (although review manuscripts are welcome as well) in the broad field of inner ear therapeutics.

Dr. Erik de Vrieze
Dr. Jennifer J. Lentz
Dr. Erwin Van Wijk
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Hearing loss
Genetic therapy
Inner ear drug delivery and biodistribution
Biomarkers and outcome measures
Nanoparticles
Regeneration

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review, Other

16 pages, 2700 KiB

Open AccessArticle

Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models

by Yu Zhao, Longlong Zhang, Daqi Wang, Bing Chen and Yilai Shu

Biomolecules 2023, 13(1), 38; https://doi.org/10.3390/biom13010038 - 26 Dec 2022

Cited by 11 | Viewed by 3352

Abstract

Inner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gene delivery approaches including posterior semicircular canal (PSCC) canalostomy, round window membrane (RWM) injection, and tubing-RWM+PSCC (t-RP) in adult mice. Transduction rates and survival rates of cochlear hair cells were analyzed, hearing function was recorded, AAV distribution in the sagittal brain sections was evaluated, and cochlear histopathologic images were appraised. We found that an injection volume of 1 μL AAV through the PSCC is safe and highly efficient and does not impair hearing function in adult mice, but local injection allows AAV vectors to spread slightly into the brain. We then tested five AAV serotypes (PHP.eB, IE, Anc80L65, AAV2, and PHP.s) in parallel and observed the most robust eGFP expression in inner hair cells, outer hair cells, and spiral ganglion neurons throughout the cochlea after AAV-Anc80L65 injection. Thus, PSCC-injected Anc80L65 provides a foundation for gene therapy in the adult cochlea and will facilitate the development of inner ear gene therapy. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

21 pages, 1056 KiB

Open AccessEditor’s ChoiceArticle

Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease

by Alexander A. Missner, James Dixon Johns, Shoujun Gu and Michael Hoa

Biomolecules 2022, 12(11), 1641; https://doi.org/10.3390/biom12111641 - 5 Nov 2022

Cited by 3 | Viewed by 2699

Abstract

Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere’s disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

23 pages, 5602 KiB

Open AccessArticle

Local Long-Term Inner Ear Drug Delivery in Normal Hearing Guinea Pig—An Animal Model to Develop Preventive Treatment for Noise-Induced Hearing Loss

by Kathrin Malfeld, Peter Baumhoff, Holger A. Volk, Thomas Lenarz and Verena Scheper

Biomolecules 2022, 12(10), 1427; https://doi.org/10.3390/biom12101427 - 5 Oct 2022

Cited by 7 | Viewed by 2783

Abstract

Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

20 pages, 5453 KiB

Open AccessArticle

Optimized AAV Vectors for TMC1 Gene Therapy in a Humanized Mouse Model of DFNB7/11

by Irina Marcovich, Nicholas K. Baer, Olga Shubina-Oleinik, Rachel Eclov, Clayton W. Beard and Jeffrey R. Holt

Biomolecules 2022, 12(7), 914; https://doi.org/10.3390/biom12070914 - 29 Jun 2022

Cited by 15 | Viewed by 4023

Abstract

Gene therapy for genetic hearing loss is an emerging therapeutic modality for hearing restoration. However, the approach has not yet been translated into clinical application. To further develop inner-ear gene therapy, we engineered a novel mouse model bearing a human mutation in the transmembrane channel-1 gene (Tmc1) and characterized the auditory phenotype of the mice. TMC1 forms the mechanosensory transduction channel in mice and humans and is necessary for auditory function. We found that mice harboring the equivalent of the human p.N199I mutation (p.N193I) had profound congenital hearing loss due to loss of hair cell sensory transduction. Next, we optimized and screened viral payloads packaged into AAV9-PHP.B capsids. The vectors were injected into the inner ears of Tmc1^Δ/Δ mice and the new humanized Tmc1-p.N193I mouse model. Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), cell survival, and biodistribution were evaluated in the injected mice. We found broad-spectrum, durable recovery of auditory function in Tmc1-p.N193I mice injected with AAV9-PHP.B-CB6-hTMC1-WPRE. ABR and DPOAE thresholds were equivalent to those of wild-type mice across the entire frequency range. Biodistribution analysis revealed viral DNA/RNA in the contralateral ear, brain, and liver but no overt toxicity. We conclude that the AAV9-PHP.B-CB6-hTMC1-WPRE construct may be suitable for further development as a gene therapy reagent for treatment of humans with genetic hearing loss due to recessive TMC1 mutations. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

9 pages, 3284 KiB

Open AccessEditor’s ChoiceArticle

Efficient Viral Transduction in Fetal and Adult Human Inner Ear Explants with AAV9-PHP.B Vectors

by Edward S. A. van Beelen, Wouter H. van der Valk, Thijs O. Verhagen, John C. M. J. de Groot, Margot A. Madison, Wijs Shadmanfar, Erik F. Hensen, Jeroen C. Jansen, Peter Paul G. van Benthem, Jeffrey R. Holt and Heiko Locher

Biomolecules 2022, 12(6), 816; https://doi.org/10.3390/biom12060816 - 10 Jun 2022

Cited by 5 | Viewed by 3172

Abstract

Numerous studies have shown the recovery of auditory function in mouse models of genetic hearing loss following AAV gene therapy, yet translation to the clinic has not yet been demonstrated. One limitation has been the lack of human inner ear cell lines or tissues for validating viral gene therapies. Cultured human inner ear tissue could help confirm viral tropism and efficacy for driving exogenous gene expression in targeted cell types, establish promoter efficacy and perhaps selectivity for targeted cells, confirm the expression of therapeutic constructs and the subcellular localization of therapeutic proteins, and address the potential cellular toxicity of vectors or exogenous constructs. To begin to address these questions, we developed an explant culture method using native human inner ear tissue excised at either fetal or adult stages. Inner ear sensory epithelia were cultured for four days and exposed to vectors encoding enhanced green fluorescent protein (eGFP). We focused on the synthetic AAV9-PHP.B capsid, which has been demonstrated to be efficient for driving eGFP expression in the sensory hair cells of mouse and non-human primate inner ears. We report that AAV9-PHP.B also drives eGFP expression in fetal cochlear hair cells and in fetal and adult vestibular hair cells in explants of human inner ear sensory epithelia, which suggests that both the experimental paradigm and the viral capsid may be valuable for translation to clinical application. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

20 pages, 4683 KiB

Open AccessArticle

3D Printed Cell Culture Chamber for Testing the Effect of Pump-Based Chronic Drug Delivery on Inner Ear Tissue

by Jana Schwieger, Anna Sophie Frisch, Thomas S. Rau, Thomas Lenarz, Silke Hügl and Verena Scheper

Biomolecules 2022, 12(4), 589; https://doi.org/10.3390/biom12040589 - 17 Apr 2022

Cited by 4 | Viewed by 3023

Abstract

Cochlear hair cell damage and spiral ganglion neuron (SGN) degeneration are the main causes of sensory neural hearing loss. Cochlear implants (CIs) can replace the function of the hair cells and stimulate the SGNs electrically. The condition of the SGNs and their spatial distance to the CI are key factors for CI-functionality. For a better performance, a high number of neurons and a closer contact to the electrode are intended. Neurotrophic factors are able to enhance SGN survival and neurite outgrowth, and thereby might optimize the electrode-nerve interaction. This would require chronic factor treatment, which is not yet established for the inner ear. Investigations on chronic drug delivery to SGNs could benefit from an appropriate in vitro model. Thus, an inner ear inspired Neurite Outgrowth Chamber (NOC), which allows the incorporation of a mini-osmotic pump for long-term drug delivery, was designed and three-dimensionally printed. The NOC’s function was validated using spiral ganglion explants treated with ciliary neurotrophic factor, neurotrophin-3, or control fluid released via pumps over two weeks. The NOC proved to be suitable for explant cultivation and observation of pump-based drug delivery over the examined period, with neurotrophin-3 significantly increasing neurite outgrowth compared to the other groups. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

19 pages, 2584 KiB

Open AccessArticle

Transcriptome-Guided Identification of Drugs for Repurposing to Treat Age-Related Hearing Loss

by Nick M. A. Schubert, Marcel van Tuinen and Sonja J. Pyott

Biomolecules 2022, 12(4), 498; https://doi.org/10.3390/biom12040498 - 25 Mar 2022

Cited by 10 | Viewed by 4033

Abstract

Age-related hearing loss (ARHL) or presbycusis is a prevalent condition associated with social isolation, cognitive impairment, and dementia. Age-related changes in the cochlea, the auditory portion of the inner ear, are the primary cause of ARHL. Unfortunately, there are currently no pharmaceutical approaches to treat ARHL. To examine the biological processes underlying age-related changes in the cochlea and identify candidate drugs for rapid repurposing to treat ARHL, we utilized bulk RNA sequencing to obtain transcriptomes from the functional substructures of the cochlea—the sensorineural structures, including the organ of Corti and spiral ganglion neurons (OC/SGN) and the stria vascularis and spiral ligament (SV/SL)—in young (6-week-old) and old (2-year-old) C57BL/6 mice. Transcriptomic analyses revealed both overlapping and unique patterns of gene expression and gene enrichment between substructures and with ageing. Based on these age-related transcriptional changes, we queried the protein products of genes differentially expressed with ageing in DrugBank and identified 27 FDA/EMA-approved drugs that are suitable to be repurposed to treat ARHL. These drugs target the protein products of genes that are differentially expressed with ageing uniquely in either the OC/SGN or SV/SL and that interrelate diverse biological processes. Further transcriptomic analyses revealed that most genes differentially expressed with ageing in both substructures encode protein products that are promising drug target candidates but are, nevertheless, not yet linked to approved drugs. Thus, with this study, we apply a novel approach to characterize the druggable genetic landscape for ARHL and propose a list of drugs to test in pre-clinical studies as potential treatment options for ARHL. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

14 pages, 1347 KiB

Open AccessEditor’s ChoiceArticle

Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro

by Ziwen Gao, Jana Schwieger, Farnaz Matin-Mann, Peter Behrens, Thomas Lenarz and Verena Scheper

Biomolecules 2021, 11(12), 1896; https://doi.org/10.3390/biom11121896 - 17 Dec 2021

Cited by 13 | Viewed by 3848

Abstract

Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C₂₂H₂₉FO₅) and dexamethasone dihydrogen phosphate-disodium (DPS, C₂₂H₂₈FNa₂O₈P) were investigated for biocompatibility and bio-efficacy in vitro. The biocompatibility of each dexamethasone formulation in concentrations from 0.03 to 10,000 µM was evaluated using an MTT assay. The concentrations resulting in the highest cell viability were selected to perform a bio-efficiency test using a TNFα-reduction assay. All dexamethasone formulations up to 900 µM are biocompatible in vitro. DPS-lab becomes toxic at 1000 µM and DPS-med at 2000 µM, while DEX-lab and DEX-med become toxic at 4000 µM. Bio-efficacy was evaluated for DEX-lab and DPS-med at 300 µM, for DEX-med at 60 µM, and DPS-lab at 150 µM, resulting in significantly reduced expression of TNFα, with DPS-lab having the highest effect. Different dexamethasone formulations need to be applied in different concentration ranges to be biocompatible. The concentration to be applied in future studies should carefully be chosen based on the respective dexamethasone form, application route and duration to ensure biocompatibility and bio-efficacy. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

Review

Jump to: Research, Other

18 pages, 372 KiB

Open AccessReview

Conversations in Cochlear Implantation: The Inner Ear Therapy of Today

by Grant Rauterkus, Anne K. Maxwell, Jacob B. Kahane, Jennifer J. Lentz and Moises A. Arriaga

Biomolecules 2022, 12(5), 649; https://doi.org/10.3390/biom12050649 - 29 Apr 2022

Cited by 6 | Viewed by 3203

Abstract

As biomolecular approaches for hearing restoration in profound sensorineural hearing loss evolve, they will be applied in conjunction with or instead of cochlear implants. An understanding of the current state-of-the-art of this technology, including its advantages, disadvantages, and its potential for delivering and interacting with biomolecular hearing restoration approaches, is helpful for designing modern hearing-restoration strategies. Cochlear implants (CI) have evolved over the last four decades to restore hearing more effectively, in more people, with diverse indications. This evolution has been driven by advances in technology, surgery, and healthcare delivery. Here, we offer a practical treatise on the state of cochlear implantation directed towards developing the next generation of inner ear therapeutics. We aim to capture and distill conversations ongoing in CI research, development, and clinical management. In this review, we discuss successes and physiological constraints of hearing with an implant, common surgical approaches and electrode arrays, new indications and outcome measures for implantation, and barriers to CI utilization. Additionally, we compare cochlear implantation with biomolecular and pharmacological approaches, consider strategies to combine these approaches, and identify unmet medical needs with cochlear implants. The strengths and weaknesses of modern implantation highlighted here can mark opportunities for continued progress or improvement in the design and delivery of the next generation of inner ear therapeutics. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

Other

Jump to: Research, Review

13 pages, 700 KiB

Open AccessSystematic Review

Inner Ear Pharmacotherapy for Residual Hearing Preservation in Cochlear Implant Surgery: A Systematic Review

by Quentin-Alexandre Parys, Pauline Van Bulck, Elke Loos and Nicolas Verhaert

Biomolecules 2022, 12(4), 529; https://doi.org/10.3390/biom12040529 - 31 Mar 2022

Cited by 12 | Viewed by 2932

Abstract

Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Figure 1

17 pages, 1935 KiB

Open AccessSystematic Review

Genotype-Phenotype Correlations of Pathogenic COCH Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis

by Sybren M. M. Robijn, Jeroen J. Smits, Kadriye Sezer, Patrick L. M. Huygen, Andy J. Beynon, Erwin van Wijk, Hannie Kremer, Erik de Vrieze, Cornelis P. Lanting and Ronald J. E. Pennings

Biomolecules 2022, 12(2), 220; https://doi.org/10.3390/biom12020220 - 27 Jan 2022

Cited by 7 | Viewed by 4537

Abstract

Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH. Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions. Full article

(This article belongs to the Special Issue Inner Ear Therapeutics)

► Show Figures

Journal Menu

Journal Browser

Inner Ear Therapeutics

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI