Research

https://www.mdpi.com/1660-4601/16/18/3428

Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss
by Sang Hyun Kwak 1,Gi-Sung Nam 2,Seong Hoon Bae 1 andJinsei Jung 1,*OrcID
1
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Korea
2
Department of Otorhinolaryngology, Chonbuk National University College of Medicine, Jeonju 54907, Korea
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2019, 16(18), 3428; https://doi.org/10.3390/ijerph16183428
Received: 3 July 2019 / Revised: 10 September 2019 / Accepted: 11 September 2019 / Published: 16 September 2019
(This article belongs to the Special Issue Environmental Exposures and Hearing Loss)

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221713

https://www.ncbi.nlm.nih.gov/pubmed/31498809?dopt=Abstract

A systematic review and network meta-analysis of existing pharmacologic therapies in patients with idiopathic sudden sensorineural hearing loss.

PLoS One. 2019;14(9):e0221713

Authors: Ahmadzai N, Kilty S, Cheng W, Esmaeilisaraji L, Wolfe D, Bonaparte JP, Schramm D, Fitzpatrick E, Lin V, Skidmore B, Moher D, Hutton B

Abstract

BACKGROUND: Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL.

METHODS: A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery.

RESULTS: The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo.

CONCLUSION: Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.

PMID: 31498809 [PubMed – in process]

https://journals.lww.com/otology-neurotology/Abstract/publishahead/High_Dose_of_Intratympanic_Steroids_for_Sudden.96374.aspx

https://www.ncbi.nlm.nih.gov/pubmed/31498293?dopt=Abstract

High Dose of Intratympanic Steroids for Sudden Sensorineural Hearing Loss Salvage.

Otol Neurotol. 2019 Sep 06;:

Authors: Taha A, Shlamkovitch N, Abu-Eta R, Yeheskeli E, Muallem-Kalmovich L, Gavriel H, Pitaro J

Abstract

OBJECTIVE: Intratympanic (IT) steroid administration for sudden sensorineural hearing loss is offered as salvage to patients who failed systemic steroid treatment. Our objective was to study the audiometric and clinical outcomes of patients given salvage therapy with high-dose IT steroids instilled via ventilation tube.

STUDY DESIGN: Retrospective case review.

SETTING: Academic secondary medical center.

PATIENTS: One hundred three patients >18 years of age with sudden sensorineural hearing loss who failed systemic steroids and received IT treatment between 2010 and 2018.

INTERVENTION: Following ventilation tube insertion, 1 ml of 10 mg/ml dexamethasone was instilled, twice daily, for 7 days.

OUTCOME MEASURES: Hearing assessment immediately before and after treatment. Tinnitus and vertigo complaints and risk factors were also retrieved.

RESULTS: Tinnitus had improved in 53 (52%) patients, vertigo in 4 (4%), and aural fullness sensation in 56 (55%) (p < 0.001, p = 0.344, p < 0.001, respectively). The mean pure-tone threshold difference across frequencies following treatment was between 0 and 6 dB. A significant improvement was observed at 250, 500, 1000 Hz (p < 0.001 in all), and at 2000 Hz (p = 0.035). No significant difference was found at 4000 and 8000 Hz (p = 0.055, p = 0.983 respectively). Mean pure-tone average improvement of 4.5 dB was detected in 61 (59%) patients (p = 0.001). The mean speech discrimination score improved by 7% (p = 0.001). Four (22%) diabetic and nine (20%) hypertensive patients had pure-tone average ≥10 dB improvement (p = 0.759, p = 0.852 respectively). CONCLUSION: Although more than half of the patients improved clinically, the significance of the slight audiometric improvement should be weighed against the treatment protocol's complications. PMID: 31498293 [PubMed - as supplied by publisher]

https://www.tandfonline.com/doi/abs/10.1080/00016489.2019.1654130?journalCode=ioto20

https://www.ncbi.nlm.nih.gov/pubmed/31486693?dopt=Abstract

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Canalostomy is an ideal surgery route for inner ear gene delivery in big animal model.

Acta Otolaryngol. 2019 Sep 05;:1-9

Authors: Ji XJ, Chen W, Wang X, Zhang Y, Liu Q, Guo WW, Zhao JG, Yang SM

Abstract

Background: Inner gene therapy offers great promises as a potential treatment for hearing loss. Aims/objectives: One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. Material and methods: Surgery was performed only in the right ear of each Bama miniature pig, and the left ear served as a control. The gene delivery to inner ear via round window membrane (RWM) and posterior semicircular canal (PSC) approach was performed with the viral vector AAV1-CMV-GFP. Results: The gene delivery through RWM and the PSC (canalostomy) is able to perfuse the inner ear. Conclusions and significance: The easy anatomic identification of the PSC, as to RWM, as well as minimal manipulation of the temporal bone required, make this surgical approach an attractive option for inner ear gene delivery in big animal model.

PMID: 31486693 [PubMed – as supplied by publisher]

https://www.nature.com/articles/s41598-019-49133-w

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Cochlear Glucocorticoid Receptor and Serum Corticosterone Expression in a Rodent Model of Noise-induced Hearing Loss: Comparison of Timing of Dexamethasone Administration.

Sci Rep. 2019 Sep 02;9(1):12646

Authors: Lee SH, Lyu AR, Shin SA, Jeong SH, Lee SA, Park MJ, Park YH

Abstract

Glucocorticoid (GC) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DEX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. In the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression.

PMID: 31477769 [PubMed – in process]

https://www.jkmood.org/archive/view_article?pid=jkmood-32-3-212

Three Cases of Sudden Sensorineural Hearing Loss with Complete Recovery by Korean Medical Treatment

https://www.nature.com/articles/s41467-019-11712-w

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PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing.

Nat Commun. 2019 Aug 23;10(1):3801

Authors: Wu X, Ivanchenko MV, Al Jandal H, Cicconet M, Indzhykulian AA, Corey DP

Abstract

The bundle of stereocilia on inner ear hair cells responds to subnanometer deflections produced by sound or head movement. Stereocilia are interconnected by a variety of links and also carry an electron-dense surface coat. The coat may contribute to stereocilia adhesion or protect from stereocilia fusion, but its molecular identity remains unknown. From a database of hair-cell-enriched translated proteins, we identify Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1), a large, mostly extracellular protein of 4249 amino acids with a single transmembrane domain. Using serial immunogold scanning electron microscopy, we show that PKHD1L1 is expressed at the tips of stereocilia, especially in the high-frequency regions of the cochlea. PKHD1L1-deficient mice lack the surface coat at the upper but not lower regions of stereocilia, and they develop progressive hearing loss. We conclude that PKHD1L1 is a component of the surface coat and is required for normal hearing in mice.

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Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment.

Exp Mol Med. 2019 Aug 21;51(8):99

Authors: Jung J, Lin H, Koh YI, Ryu K, Lee JS, Rim JH, Choi HJ, Lee HJ, Kim HY, Yu S, Jin H, Lee JH, Lee MG, Namkung W, Choi JY, Gee HY

Abstract

KCNQ4 is frequently mutated in autosomal dominant non-syndromic hearing loss (NSHL), a typically late-onset, initially high-frequency loss that progresses over time (DFNA2). Most KCNQ4 mutations linked to hearing loss are clustered around the pore region of the protein and lead to loss of KCNQ4-mediated potassium currents. To understand the contribution of KCNQ4 variants to NSHL, we surveyed public databases and found 17 loss-of-function and six missense KCNQ4 variants affecting amino acids around the pore region. The missense variants have not been reported as pathogenic and are present at a low frequency (minor allele frequency < 0.0005) in the population. We examined the functional impact of these variants, which, interestingly, induced a reduction in potassium channel activity without altering expression or trafficking of the channel protein, being functionally similar to DFNA2-associated KCNQ4 mutations. Therefore, these variants may be risk factors for late-onset hearing loss, and individuals harboring any one of these variants may develop hearing loss during adulthood. Reduced channel activity could be rescued by KCNQ activators, suggesting the possibility of medical intervention. These findings indicate that KCNQ4 variants may contribute more to late-onset NSHL than expected, and therefore, genetic screening for this gene is important for the prevention and treatment of NSHL. PMID: 31434872 [PubMed - in process]

https://www.sciencedirect.com/science/article/pii/S0378595519301893?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31493568?dopt=Abstract

Cochlear histopathology in human genetic hearing loss: State of the science and future prospects.

Hear Res. 2019 Aug 19;382:107785

Authors: Bommakanti K, Iyer JS, Stankovic KM

Abstract

Sensorineural hearing loss (SNHL) is an extraordinarily common disability, affecting 466 million people across the globe. Half of these incidents are attributed to genetic mutations that disrupt the structure and function of the cochlea. The human cochlea’s interior cannot be imaged or biopsied without damaging hearing; thus, everything known about the morphologic correlates of hereditary human deafness comes from histopathologic studies conducted in either cadaveric human temporal bone specimens or animal models of genetic deafness. The purpose of the present review is to a) summarize the findings from all published histopathologic studies conducted in human temporal bones with known SNHL-causing genetic mutations, and b) compare the reported phenotypes of human vs. mouse SNHL caused by the same genetic mutation. The fact that human temporal bone histopathologic analysis has been reported for only 22 of the nearly 200 identified deafness-causing genes suggests a great need for alternative and improved techniques for studying human hereditary deafness; in light of this, the present review concludes with a summary of promising future directions, specifically in the fields of high resolution cochlear imaging, intracochlear fluid biopsy, and gene therapy.

PMID: 31493568 [PubMed – as supplied by publisher]

https://www.termedia.pl/Hearing-regeneration-and-regenerative-medicine-present-and-future-approaches,19,36991,1,1.html

https://www.ncbi.nlm.nih.gov/pubmed/31360190?dopt=Abstract

Hearing regeneration and regenerative medicine: present and future approaches.

Arch Med Sci. 2019 Jul;15(4):957-967

Authors: Nacher-Soler G, Garrido JM, Rodríguez-Serrano F

Abstract

More than 5% of the world population lives with a hearing impairment. The main factors responsible for hearing degeneration are ototoxic drugs, aging, continued exposure to excessive noise and infections. The pool of adult stem cells in the inner ear drops dramatically after birth, and therefore an endogenous cellular source for regeneration is absent. Hearing loss can emerge after the degeneration of different cochlear components, so there are multiple targets to be reached, such as hair cells (HCs), spiral ganglion neurons (SGNs), supporting cells (SCs) and ribbon synapses. Important discoveries in the hearing regeneration field have been reported regarding stem cell transplantation, migration and survival; genetic systems for cell fate monitoring; and stem cell differentiation to HCs, SGNs and SCs using adult stem cells, embryonic stem cells and induced pluripotent stem cells. Moreover, some molecular mediators that affect the establishment of functional synapses have been identified. In this review, we will focus on reporting the state of the art in the regenerative medicine field for hearing recovery. Stem cell research has enabled remarkable advances in regeneration, particularly in neuronal cells and synapses. Despite the progress achieved, there are certain issues that need a deeper development to improve the results already obtained, or to develop new approaches aiming for the clinical application.

PMID: 31360190 [PubMed]

https://www.nature.com/articles/s41420-019-0195-1

https://www.ncbi.nlm.nih.gov/pubmed/31312524?dopt=Abstract

Avenanthramide-C prevents noise- and drug-induced hearing loss while protecting auditory hair cells from oxidative stress.

Cell Death Discov. 2019;5:115

Authors: Umugire A, Lee S, Kim D, Choi M, Kim HS, Cho HH

Abstract

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24โ€‰h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (Kโ€‰+โ€‰F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to Kโ€‰+โ€‰F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.

PMID: 31312524 [PubMed]

https://www.ncbi.nlm.nih.gov/pubmed/31285299?dopt=Abstract

Divergent auditory-nerve encoding deficits between two common etiologies of sensorineural hearing loss.

J Neurosci. 2019 Jul 08;:

Authors: Henry KS, Sayles M, Hickox AE, Heinz MG

Abstract

Speech intelligibility can vary dramatically between individuals with similar clinically defined severity of hearing loss based on the audiogram. These perceptual differences, despite equal audiometric-threshold elevation, are often assumed to reflect central-processing variations. Here, we compared peripheral-processing in auditory-nerve fibers of male chinchillas between two prevalent hearing-loss etiologies: metabolic hearing loss (MHL) and noise-induced hearing loss (NIHL). MHL results from age-related reduction of the endocochlear potential due to atrophy of the stria vascularis. MHL in the present study was induced using furosemide, which provides a validated model of age-related MHL in young animals by reversibly inhibiting the endocochlear potential. Effects of MHL on peripheral processing were assessed using Wiener-kernel (system-identification) analyses of single auditory-nerve fiber responses to broadband noise, for direct comparison to previously published auditory-nerve responses from animals with NIHL. Wiener-kernel analyses show that even mild NIHL causes grossly abnormal coding of low-frequency stimulus components. In contrast, for MHL the same abnormal coding was only observed with moderate-severe loss. For equal sensitivity loss, coding impairment was substantially less severe with MHL than with NIHL, probably due to greater preservation of the tip-to-tail ratio of cochlear frequency tuning with MHL compared to NIHL rather than different intrinsic auditory-nerve properties. Differences in peripheral neural coding between these two pathologies [sbond] the more severe of which, NIHL, is preventable [sbond] likely contribute to individual speech-perception differences. Our results underscore the need to minimize noise overexposure and for strategies to personalize diagnosis and treatment for individuals with sensorineural hearing loss.SIGNIFICANCE STATEMENTDifferences in speech perception ability between individuals with similar clinically defined severity of hearing loss are often assumed to reflect central neural processing differences. Here, we demonstrate for the first time that peripheral neural processing of complex sounds differs dramatically between the two most common etiologies of hearing loss. Greater processing impairment with noise-induced compared to an age-related (metabolic) hearing-loss etiology may explain heightened speech-perception difficulties in people overexposed to loud environments. These results highlight the need for public policies to prevent noise-induced hearing loss – an entirely avoidable hearing-loss etiology – and for personalized strategies to diagnose and treat sensorineural hearing loss.

PMID: 31285299 [PubMed – as supplied by publisher]

https://www.sciencedirect.com/science/article/pii/S0378595518305343

Early phase trials of novel hearing therapeutics: Avenues and opportunities

https://asa.scitation.org/doi/10.1121/1.5111870

https://www.ncbi.nlm.nih.gov/pubmed/31255106?dopt=Abstract

Sex differences in hearing: Probing the role of estrogen signaling.

J Acoust Soc Am. 2019 Jun;145(6):3656

Authors: Shuster BZ, Depireux DA, Mong JA, Hertzano R

Abstract

Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans. While hearing loss affects both men and women, sexual dimorphism is documented with respect to peripheral and central auditory physiology, as well as susceptibility to age-related and noise-induced hearing loss. Physiological differences between the sexes are often hormone-driven, and an increasing body of literature demonstrates that the hormone estrogen and its related signaling pathways may in part, modulate the aforementioned differences in hearing. From a mechanistic perspective, understanding the underpinnings of the hormonal modulation of hearing may lead to the development of therapeutics for age related and noise induced hearing loss. Here the authors review a number of studies that range from human populations to animal models, which have begun to provide a framework for understanding the functional role of estrogen signaling in hearing, particularly in normal and aberrant peripheral auditory physiology.

PMID: 31255106 [PubMed – in process]

https://elifesciences.org/articles/47613

A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea

https://www.ncbi.nlm.nih.gov/pubmed/31122277?dopt=Abstract

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Association of anemia with sensorineural hearing loss: a systematic review and meta-analysis.

BMC Res Notes. 2019 May 23;12(1):283

Authors: Mohammed SH, Shab-Bidar S, Abuzerr S, Habtewold TD, Alizadeh S, Djafarian K

Abstract

OBJECTIVE: Evidence shows that anemic individuals are at a higher risk of hearing loss. However, there is no systematic review and meta-analysis study. Thus, we aimed to meta-analyze the existing evidence on the association of iron deficiency anemia (IDA) with sensorineural hearing loss (SNHL). We searched PubMed, MEDLINE, Embase, Scopus, and Google Scholar from inception through October 30, 2017, for studies done on the association of the IDA with SNHL. Pooled odds ratio (OR) was calculated by random effect meta-analysis method. Heterogeneity was assessed by I2 metrics.

RESULT: Four studies, covering a total of 344,080 adults and children, were included. The odds of SNHL was higher by 55% in individuals with IDA, compared with individuals without IDA (OR = 1.55, 95% CI 1.17-2.06; P = 0.03). The age-specific ORs were 1.36 (95% CI 1.15-1.61; P = 0.27) and 3.67 (95% CI 1.72-7.84) for adults and children, respectively. IDA may be a contributing factor to hearing loss. Further studies are warranted, including whether IDA treatment reduces the risk of hearing loss. Meanwhile, hearing loss screening in anemic individuals, or vice versa, may represent an important consideration. PROSPERO registration CRD42017082108.

PMID: 31122277 [PubMed – in process]

https://journals.lww.com/otology-neurotology/Abstract/2019/06000/Hearing_Protection,_Restoration,_and_Regeneration_.2.aspx

https://www.ncbi.nlm.nih.gov/pubmed/31083073?dopt=Abstract

Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders.

Otol Neurotol

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Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders.

Otol Neurotol. 2019 Jun;40(5):559-570

Authors: Schilder AGM, Su MP, Blackshaw H, Lustig L, Staecker H, Lenarz T, Safieddine S, Gomes-Santos CS, Holme R, Warnecke A

Abstract

OBJECTIVE: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches.

METHODS: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated.

RESULTS: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years.

CONCLUSION: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies’ mechanisms of action, applications, and indications.

PMID: 31083073 [PubMed – in process]

PubMed:31083073

https://www.hindawi.com/journals/mi/2019/7915730/abs/

Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression

https://www.frontiersin.org/articles/10.3389/fncel.2019.00155/full

https://www.tandfonline.com/doi/full/10.1080/21691401.2019.1573182

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Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea

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Therapeutic Potential of Wnt and Notch Signaling and Epigenetic Regulation in Mammalian Sensory Hair Cell Regeneration

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Protection of Spiral Ganglion Neurons and Prevention of Auditory Neuropathy.

Adv Exp Med Biol. 2019;1130:93-107

Authors: Liu W, Wang X, Wang M, Wang H

Abstract

In the auditory system, the primary sensory neurons, spiral ganglion neurons (SGNs), transmit complex acoustic information from hair cells to the second-order sensory neurons in the cochlear nucleus for sound processing, thus building the initial bridge between the physical world of sound and the perception of that sound. Cochlear SGN loss causes irreversible hearing impairment because this type of neural cell cannot regenerate. A better understanding of the molecular mechanisms of formation, structure, degeneration, and protection of SGNs will help to design potential therapeutic strategies for preservation and replacement of them in the cochlear implant recipient. In this review, we described and summarized the following about SGNs: (1) their cell biology and their peripheral and central connections, (2) mechanisms of their neuronal damage and their protection, and (3) the neural and synaptic mechanism of auditory neuropathy and current options for hearing rehabilitation from auditory neuropathy. The updates of the research progress and the significant issues on these topics were discussed.

PMID: 30915703 [PubMed – indexed for MEDLINE]

https://www.nature.com/articles/s41419-018-0967-1

https://www.ncbi.nlm.nih.gov/pubmed/30206231?dopt=Abstract

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Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells.

Cell Death Dis. 2018 09 11;9(9):922

Authors: Jeong M, O’Reilly M, Kirkwood NK, Al-Aama J, Lako M, Kros CJ, Armstrong L

Abstract

In view of the prevalence of sensorineural hearing defects in an ageing population, the development of protocols to generate cochlear hair cells and their associated sensory neurons as tools to further our understanding of inner ear development are highly desirable. We report herein a robust protocol for the generation of both vestibular and cochlear hair cells from human pluripotent stem cells which represents an advance over currently available methods that have been reported to generate vestibular hair cells only. Generating otic organoids from human pluripotent stem cells using a three-dimensional culture system, we show formation of both types of sensory hair cells bearing stereociliary bundles with active mechano-sensory ion channels. These cells share many morphological characteristics with their in vivo counterparts during embryonic development of the cochlear and vestibular organs and moreover demonstrate electrophysiological activity detected through single-cell patch clamping. Collectively these data represent an advance in our ability to generate cells of an otic lineage and will be useful for building models of the sensory regions of the cochlea and vestibule.

PMID: 30206231 [PubMed – indexed for MEDLINE]

https://www.ncbi.nlm.nih.gov/pubmed/30100544?dopt=Abstract

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Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss.

J Int Adv Otol. 2018 Aug;14(2):166-169

Authors: Koide Y, Teranishi M, Sugiura S, Uchida Y, Nishio N, Kato K, Otake H, Yoshida T, Otsuka R, Ando F, Shimokata H, Hasegawa Y, Nakashima T, Sone M

Abstract

OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk.

MATERIALS AND METHODS: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene.

RESULTS: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex.

CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.

PMID: 30100544 [PubMed – indexed for MEDLINE]

http://www.noiseandhealth.org/article.asp?issn=1463-1741;year=2018;volume=20;issue=93;spage=47;epage=52;aulast=Kum

https://www.ncbi.nlm.nih.gov/pubmed/29676295?dopt=Abstract

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Effects of parenteral papaverine and piracetam administration on cochlea following acoustic trauma.

Noise Health. 2018 Mar-Apr;20(93):47-52

Authors: Kum NY, Yilmaz YF, Gurgen SG, Kum RO, Ozcan M, Unal A

Abstract

Introduction: Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation.

Materials and Methods: Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study. We investigated the histopathologic effects of cellular apoptosis on inner hair cells (IHCs) and outer hair cells (OHCs) and compared the distortion product otoacoustic emissions (DPOAEs) thresholds among the groups.

Results and Discussion: On the 3rd and 7th days, DPOAE thresholds at 8 kHz were significantly higher both in papaverine and piracetam groups compared with the control group (P = 0.004 for 3rd day, P = 0.016 and P = 0.028 for 7th day, respectively). On the 14th day, piracetam group had significantly higher mean thresholds at 8 kHz (P = 0.029); however, papaverine group had similar mean thresholds compared to the control group (P = 0.200). On the 3rd and 7th days following acoustic trauma, both IHC and OHC loss were significantly lower in both papaverine and piracetam groups. On the 7th day, the mean amount of apoptotic IHCs and OHCs identified using Caspase-3 method were significantly lower in both groups, but the mean amount identified using terminal deoxynucleotidyl transferase dUTP nick end labeling method were similar in both groups compared to the control group.

Conclusion: We demonstrated the effects of papaverine and piracetam on the recovery of cochlear damage due to acoustic trauma on experimental animals using histopathologic and electrophysiologic examinations.

PMID: 29676295 [PubMed – indexed for MEDLINE]