Innovative Technologies and Translational Therapies for Deafness

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Otolaryngology".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 26907

Special Issue Editors


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Guest Editor
AP-HP, GHU Pitié-Salpêtrière, DMU ChIR, Service ORL, GRC Robotique et Innovation Chirurgicale, Sorbonne Université, 75006 Paris, France
Interests: deafness; inner ear; gene therapy; regeneration
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Guest Editor
Hôpital Universitaire Pitié Salpêtrière, Paris, France
Interests: deafness; inner ear; gene therapy; regeneration

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Guest Editor
Department of Otolaryngology–Head and Neck Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiatotong University, Shanghai 200011, China
Interests: deafness; cochlear nucleus; auditory pathway; central auditory prosthesis

Special Issue Information

Dear Colleagues,

Deafness and vestibular disorders are frequent pathologies, sources of disability, and can lead to impaired quality of life. Deafness is the most common sensory disorder in humans; over 5% of the world’s population require some form of hearing rehabilitation. Currently, there is no cure for sensorineural deafness, only rehabilitation techniques, including conventional hearing aids and implanted auditory prostheses, such as cochlear implants. Over the past decade, numerous groups have worked on innovative technologies and therapies for deafness, including molecular, cellular, and gene therapies. Others have developed technologies to reach the organ of Corti, the sensory organ of the inner ear, which is isolated from the rest of the body by a double bone and blood–perilymphatic barrier. However, many challenges still remain to be overcome before considering application in humans. Our goal with this Special Issue is to encourage submissions of papers that provide updates on the state of the art of current knowledge in each of the related important fields aiming towards innovative treatments for deafness.

Prof. Dr. Olivier Sterkers
Dr. Ghizlène Lahlou
Prof. Dr. Huan Jia
Guest Editors

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Keywords

  • deafness
  • inner ear
  • gene therapy
  • regeneration
  • pharmacokinetics
  • delivery systems
  • robot-assistance
  • central auditory prosthesis

Published Papers (10 papers)

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Research

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14 pages, 2948 KiB  
Article
Audiovisual Training in Virtual Reality Improves Auditory Spatial Adaptation in Unilateral Hearing Loss Patients
by Mariam Alzaher, Chiara Valzolgher, Grégoire Verdelet, Francesco Pavani, Alessandro Farnè, Pascal Barone and Mathieu Marx
J. Clin. Med. 2023, 12(6), 2357; https://doi.org/10.3390/jcm12062357 - 17 Mar 2023
Cited by 4 | Viewed by 1657
Abstract
Unilateral hearing loss (UHL) leads to an alteration of binaural cues resulting in a significant increment of spatial errors in the horizontal plane. In this study, nineteen patients with UHL were recruited and randomized in a cross-over design into two groups; a first [...] Read more.
Unilateral hearing loss (UHL) leads to an alteration of binaural cues resulting in a significant increment of spatial errors in the horizontal plane. In this study, nineteen patients with UHL were recruited and randomized in a cross-over design into two groups; a first group (n = 9) that received spatial audiovisual training in the first session and a non-spatial audiovisual training in the second session (2 to 4 weeks after the first session). A second group (n = 10) received the same training in the opposite order (non-spatial and then spatial). A sound localization test using head-pointing (LOCATEST) was completed prior to and following each training session. The results showed a significant decrease in head-pointing localization errors after spatial training for group 1 (24.85° ± 15.8° vs. 16.17° ± 11.28°; p < 0.001). The number of head movements during the spatial training for the 19 participants did not change (p = 0.79); nonetheless, the hand-pointing errors and reaction times significantly decreased at the end of the spatial training (p < 0.001). This study suggests that audiovisual spatial training can improve and induce spatial adaptation to a monaural deficit through the optimization of effective head movements. Virtual reality systems are relevant tools that can be used in clinics to develop training programs for patients with hearing impairments. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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17 pages, 4562 KiB  
Article
Optical Coherence Tomography-Based Atlas of the Human Cochlear Hook Region
by Lore Kerkhofs, Anastasiya Starovoyt, Jan Wouters, Tristan Putzeys and Nicolas Verhaert
J. Clin. Med. 2023, 12(1), 238; https://doi.org/10.3390/jcm12010238 - 28 Dec 2022
Viewed by 2044
Abstract
Advancements in intracochlear diagnostics, as well as prosthetic and regenerative inner ear therapies, rely on a good understanding of cochlear microanatomy. The human cochlea is very small and deeply embedded within the densest skull bone, making nondestructive visualization of its internal microstructures extremely [...] Read more.
Advancements in intracochlear diagnostics, as well as prosthetic and regenerative inner ear therapies, rely on a good understanding of cochlear microanatomy. The human cochlea is very small and deeply embedded within the densest skull bone, making nondestructive visualization of its internal microstructures extremely challenging. Current imaging techniques used in clinical practice, such as MRI and CT, fall short in their resolution to visualize important intracochlear landmarks, and histological analysis of the cochlea cannot be performed on living patients without compromising their hearing. Recently, optical coherence tomography (OCT) has been shown to be a promising tool for nondestructive micrometer resolution imaging of the mammalian inner ear. Various studies performed on human cadaveric tissue and living animals demonstrated the ability of OCT to visualize important cochlear microstructures (scalae, organ of Corti, spiral ligament, and osseous spiral lamina) at micrometer resolution. However, the interpretation of human intracochlear OCT images is non-trivial for researchers and clinicians who are not yet familiar with this novel technology. In this study, we present an atlas of intracochlear OCT images, which were acquired in a series of 7 fresh and 10 fresh-frozen human cadaveric cochleae through the round window membrane and describe the qualitative characteristics of visualized intracochlear structures. Likewise, we describe several intracochlear abnormalities, which could be detected with OCT and are relevant for clinical practice. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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10 pages, 3267 KiB  
Article
Robotized Cochlear Implantation under Fluoroscopy: A Preliminary Series
by Thierry Mom, Mathilde Puechmaille, Mohamed El Yagoubi, Alexane Lère, Jens-Erik Petersen, Justine Bécaud, Nicolas Saroul, Laurent Gilain, Sonia Mirafzal and Pascal Chabrot
J. Clin. Med. 2023, 12(1), 211; https://doi.org/10.3390/jcm12010211 - 27 Dec 2022
Cited by 1 | Viewed by 1568
Abstract
It is known that visual feedback by fluoroscopy can detect electrode array (EA) misrouting within the cochlea while robotized EA-insertion (rob-EAI) permits atraumatic cochlear implantation. We report here our unique experience of both fluoroscopy feedback and rob-EAI in cochlear implant surgery. We retrospectively [...] Read more.
It is known that visual feedback by fluoroscopy can detect electrode array (EA) misrouting within the cochlea while robotized EA-insertion (rob-EAI) permits atraumatic cochlear implantation. We report here our unique experience of both fluoroscopy feedback and rob-EAI in cochlear implant surgery. We retrospectively analyzed a cohort of consecutive patients implanted from November 2021–October 2022 using rob-EAI, with the RobOtol®, to determine the quality of EA-insertion and the additional time required. Twenty-three patients (10 females, 61+/−19 yo) were tentatively implanted using robot assistance, with a rob-EAI speed < 1 mm/s. Only three cases required a successful revised insertion by hand. Under fluoroscopy (n = 11), it was possible to achieve a remote rob-EAI (n = 8), as the surgeon was outside the operative room, behind an anti-radiation screen. No scala translocation occurred. The additional operative time due to robot use was 18+/−7 min with about 4 min more for remote rob-EAI. Basal cochlear turn fibrosis precluded rob-EAI. In conclusion, Rob-EAI can be performed in almost all cases with a low risk of scala translocation, except in the case of partial cochlear obstruction such as fibrosis. Fluoroscopy also permits remote rob-EAI. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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12 pages, 1147 KiB  
Article
Immediate-Early Modifications to the Metabolomic Profile of the Perilymph Following an Acoustic Trauma in a Sheep Model
by Luc Boullaud, Hélène Blasco, Eliott Caillaud, Patrick Emond and David Bakhos
J. Clin. Med. 2022, 11(16), 4668; https://doi.org/10.3390/jcm11164668 - 10 Aug 2022
Cited by 3 | Viewed by 1330
Abstract
The pathophysiological mechanisms of noise-induced hearing loss remain unknown. Identifying biomarkers of noise-induced hearing loss may increase the understanding of pathophysiological mechanisms of deafness, allow for a more precise diagnosis, and inform personalized treatment. Emerging techniques such as metabolomics can help to identify [...] Read more.
The pathophysiological mechanisms of noise-induced hearing loss remain unknown. Identifying biomarkers of noise-induced hearing loss may increase the understanding of pathophysiological mechanisms of deafness, allow for a more precise diagnosis, and inform personalized treatment. Emerging techniques such as metabolomics can help to identify these biomarkers. The objective of the present study was to investigate immediate-early changes in the perilymph metabolome following acoustic trauma. Metabolomic analysis was performed using liquid chromatography coupled to mass spectrophotometry to analyze metabolic changes in perilymph associated with noise-induced hearing loss. Sheep (n = 6) were exposed to a noise designed to induce substantial hearing loss. Perilymph was collected before and after acoustic trauma. Data were analyzed using univariate analysis and a supervised multivariate analysis based on partial least squares discriminant analysis. A metabolomic analysis showed an abundance of 213 metabolites. Four metabolites were significantly changed following acoustic trauma (Urocanate (p = 0.004, FC = 0.48), S-(5’-Adenosyl)-L-Homocysteine (p = 0.06, FC = 2.32), Trigonelline (p = 0.06, FC = 0.46) and N-Acetyl-L-Leucine (p = 0.09, FC = 2.02)). The approach allowed for the identification of new metabolites and metabolic pathways involved with acoustic trauma that were associated with auditory impairment (nerve damage, mechanical destruction, and oxidative stress). The results suggest that metabolomics provides a powerful approach to characterize inner ear metabolites which may lead to identification of new therapies and therapeutic targets. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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12 pages, 4093 KiB  
Article
Best Fit 3D Basilar Membrane Reconstruction to Routinely Assess the Scalar Position of the Electrode Array after Cochlear Implantation
by Renato Torres, Jean-Yves Tinevez, Hannah Daoudi, Ghizlene Lahlou, Neil Grislain, Eugénie Breil, Olivier Sterkers, Isabelle Mosnier, Yann Nguyen and Evelyne Ferrary
J. Clin. Med. 2022, 11(8), 2075; https://doi.org/10.3390/jcm11082075 - 7 Apr 2022
Cited by 5 | Viewed by 2308
Abstract
The scalar position of the electrode array is assumed to be associated with auditory performance after cochlear implantation. We propose a new method that can be routinely applied in clinical practice to assess the position of an electrode array. Ten basilar membrane templates [...] Read more.
The scalar position of the electrode array is assumed to be associated with auditory performance after cochlear implantation. We propose a new method that can be routinely applied in clinical practice to assess the position of an electrode array. Ten basilar membrane templates were generated using micro-computed tomography (micro-CT), based on the dimensions of 100 cochleae. Five surgeons were blinded to determine the position of the electrode array in 30 cadaveric cochleae. The procedure consisted of selecting the appropriate template based on cochlear dimensions, merging the electrode array reconstruction with the template using four landmarks, determining the position of the array according to the template position, and comparing the results obtained to histology data. The time taken to analyze each implanted cochlea was approximately 12 min. We found that, according to histology, surgeons were in almost perfect agreement when determining an electrode translocated to the scala vestibuli with the perimodiolar MidScala array (Fleiss’ kappa (κ) = 0.82), and in moderate agreement when using the lateral wall EVO array (κ = 0.42). Our data indicate that an adapted basilar membrane template can be used as a rapid and reproducible method to assess the position of the electrode array after cochlear implantation. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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Review

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19 pages, 1564 KiB  
Review
Current and Emerging Therapies for Chronic Subjective Tinnitus
by Ki Wan Park, Peter Kullar, Charvi Malhotra and Konstantina M. Stankovic
J. Clin. Med. 2023, 12(20), 6555; https://doi.org/10.3390/jcm12206555 - 16 Oct 2023
Cited by 2 | Viewed by 4639
Abstract
Importance: Chronic subjective tinnitus, the perception of sound without an external source for longer than six months, may be a greatly debilitating condition for some people, and is associated with psychiatric comorbidities and high healthcare costs. Current treatments are not beneficial for all [...] Read more.
Importance: Chronic subjective tinnitus, the perception of sound without an external source for longer than six months, may be a greatly debilitating condition for some people, and is associated with psychiatric comorbidities and high healthcare costs. Current treatments are not beneficial for all patients and there is a large need for new therapies for tinnitus. Observations: Unlike rarer cases of objective tinnitus, chronic subjective tinnitus often has no obvious etiology and a diverse pathophysiology. In the absence of objective testing, diagnosis is heavily based on clinical assessment. Management strategies include hearing aids, sound masking, tinnitus retraining therapy, cognitive behavioral therapy, and emerging therapies including transcranial magnetic stimulation and electrical stimulation. Conclusions and relevance: Although current treatments are limited, emerging diagnostics and treatments provide promising avenues for the management of tinnitus symptoms. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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19 pages, 1807 KiB  
Review
Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder
by Anissa Rym Saidia, Jérôme Ruel, Amel Bahloul, Benjamin Chaix, Frédéric Venail and Jing Wang
J. Clin. Med. 2023, 12(3), 738; https://doi.org/10.3390/jcm12030738 - 17 Jan 2023
Cited by 4 | Viewed by 5178
Abstract
Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by an impaired transmission of sound from the cochlea to the brain. This defect can be due to a lesion or defect in the inner hair cell (IHC), IHC ribbon [...] Read more.
Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by an impaired transmission of sound from the cochlea to the brain. This defect can be due to a lesion or defect in the inner hair cell (IHC), IHC ribbon synapse (e.g., pre-synaptic release of glutamate), postsynaptic terminals of the spiral ganglion neurons, or demyelination and axonal loss within the auditory nerve. To date, the only clinical treatment options for ANSD are hearing aids and cochlear implantation. However, despite the advances in hearing-aid and cochlear-implant technologies, the quality of perceived sound still cannot match that of the normal ear. Recent advanced genetic diagnostics and clinical audiology made it possible to identify the precise site of a lesion and to characterize the specific disease mechanisms of ANSD, thus bringing renewed hope to the treatment or prevention of auditory neurodegeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes to repair damaged cells for the future restoration of hearing in deaf people are showing promise. In this review, we provide an update on recent discoveries in the molecular pathophysiology of genetic lesions, auditory synaptopathy and neuropathy, and gene-therapy research towards hearing restoration in rodent models and in clinical trials. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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18 pages, 829 KiB  
Review
Extracellular Vesicles in Inner Ear Therapies—Pathophysiological, Manufacturing, and Clinical Considerations
by Athanasia Warnecke, Hinrich Staecker, Eva Rohde, Mario Gimona, Anja Giesemann, Agnieszka J. Szczepek, Arianna Di Stadio, Ingeborg Hochmair and Thomas Lenarz
J. Clin. Med. 2022, 11(24), 7455; https://doi.org/10.3390/jcm11247455 - 15 Dec 2022
Cited by 4 | Viewed by 2281
Abstract
(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on [...] Read more.
(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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11 pages, 3041 KiB  
Review
Inner Ear Diagnostics and Drug Delivery via Microneedles
by Stephen Leong, Aykut Aksit, Sharon J. Feng, Jeffrey W. Kysar and Anil K. Lalwani
J. Clin. Med. 2022, 11(18), 5474; https://doi.org/10.3390/jcm11185474 - 17 Sep 2022
Cited by 4 | Viewed by 1831
Abstract
Objectives: Precision medicine for inner ear disorders has seen significant advances in recent years. However, unreliable access to the inner ear has impeded diagnostics and therapeutic delivery. The purpose of this review is to describe the development, production, and utility of novel microneedles [...] Read more.
Objectives: Precision medicine for inner ear disorders has seen significant advances in recent years. However, unreliable access to the inner ear has impeded diagnostics and therapeutic delivery. The purpose of this review is to describe the development, production, and utility of novel microneedles for intracochlear access. Methods: We summarize the current work on microneedles developed using two-photon polymerization (2PP) lithography for perforation of the round window membrane (RWM). We contextualize our findings with the existing literature in intracochlear diagnostics and delivery. Results: Two-photon polymerization lithography produces microneedles capable of perforating human and guinea pig RWMs without structural or functional damage. Solid microneedles may be used to perforate guinea pig RWMs in vivo with full reconstitution of the membrane in 48–72 h, and hollow microneedles may be used to aspirate perilymph or inject therapeutics into the inner ear. Microneedles produced with two-photon templated electrodeposition (2PTE) have greater strength and biocompatibility and may be used to perforate human RWMs. Conclusions: Microneedles produced with 2PP lithography and 2PTE can safely and reliably perforate the RWM for intracochlear access. This technology is groundbreaking and enabling in the field of inner ear precision medicine. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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13 pages, 625 KiB  
Review
A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics
by Madeleine St. Peter, Athanasia Warnecke and Hinrich Staecker
J. Clin. Med. 2022, 11(2), 316; https://doi.org/10.3390/jcm11020316 - 9 Jan 2022
Cited by 4 | Viewed by 2574
Abstract
In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold [...] Read more.
In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss. Full article
(This article belongs to the Special Issue Innovative Technologies and Translational Therapies for Deafness)
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