Bone-anchored Hearing Aids in Unilateral Inner Ear Deafness

AbstractSensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.

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mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

International Journal of Molecular Sciences ◽

10.3390/ijms22126368 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6368

Author(s):

Maurizio Cortada ◽

Soledad Levano ◽

Daniel Bodmer

Keyword(s):

Hearing Loss ◽

Cell Survival ◽

Inner Ear ◽

Hearing Aids ◽

Noise Exposure ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Curative Therapy ◽

Age Related ◽

Survival Pathways

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

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Bone-anchored hearing aid in unilateral inner ear deafness: electrophysiological results in patients following vestibular schwannoma removal

Acta Oto-Laryngologica ◽

10.1080/00016480801901642 ◽

2008 ◽

Vol 128 (11) ◽

pp. 1203-1210 ◽

Cited By ~ 9

Author(s):

Stephane Tringali ◽

Alexandre Marzin ◽

Christian Dubreuil ◽

Chantal Ferber-Viart

Keyword(s):

Inner Ear ◽

Vestibular Schwannoma ◽

Hearing Aid ◽

Bone Anchored Hearing Aid ◽

Inner Ear Deafness

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Inner Ear Deafness

Encyclopedia of Otolaryngology, Head and Neck Surgery ◽

10.1007/978-3-642-23499-6_100502 ◽

2013 ◽

pp. 1331-1331

Keyword(s):

Inner Ear ◽

Inner Ear Deafness

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Viral Causes of Sudden inner Ear Deafness

Otolaryngologic Clinics of North America ◽

10.1016/s0030-6665(20)32571-8 ◽

1978 ◽

Vol 11 (1) ◽

pp. 63-69 ◽

Cited By ~ 5

Author(s):

Burton F. Jaffe

Keyword(s):

Inner Ear ◽

Inner Ear Deafness

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New insights in cisplatin and radiation-induced ototoxicity: A French Childhood Cancer Survivors Study (FCCSS).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.10061 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 10061-10061 ◽

Cited By ~ 1

Author(s):

Brice Fresneau ◽

Felicia Santos ◽

Rodrigue Allodji ◽

Chiraz Fayech ◽

Stephanie Bolle ◽

...

Keyword(s):

Risk Factors ◽

Cancer Survivors ◽

Childhood Cancer ◽

Inner Ear ◽

Hearing Aids ◽

Social Deprivation ◽

Childhood Cancer Survivors ◽

Solid Cancer ◽

Cranial Radiotherapy

10061 Background: Platinum chemotherapy (CT) and cranial radiotherapy (RT) are risk factors of ototoxicity. Effects of RT dose at inner ear and of other CT were investigated. Methods: Of 7670 5-year childhood cancer survivors from the FCCSS treated before 20 years of age in 1942-2000 for solid cancer or lymphoma, 5243 with ototoxicity long-term follow-up data were included. Severe ototoxicity, defined as the need of hearing aids or Brock grade 3-4 hearing loss, was identified from self-administrated questionnaires, clinical visits and cohort linkage with the French Hospital Database and health insurance information system (SNIIRAM). The mean RT dose at inner ear was estimated using home-made software. Multivariable Cox models adjusted for gender, age at diagnosis, time period and social deprivation index was used to identify risk factors for severe ototoxicity. Results: After a mean follow-up of 30 years, 199 cases of severe ototoxicity were identified. Cumulative incidences at 30 and 50 years of age (30,50y-CumInc) were, 2.8% (95%CI = 2.4-3.3) and 5.5% (4.6-6.5), respectively. Mean RT dose at inner ear (Hazard Ratio HR = 1.6 (95%CI = 1.0-2.5), 4.5 (2.7-7.2), 5.7 (3.0-10.8) and 14.0 (9.2-21.2) for 0- < 5, 5- < 30, 30- < 40 and ≥40 Gy), as well as cisplatin (HR = 2.8, 95%CI = 1.9-4.0), melphalan (HR = 3.3, 95%CI = 1.9-5.7) and busulfan exposure (HR = 2.6, 95%CI = 1.6-4.4) were significantly associated with severe ototoxicity. Concerning melphalan (n = 199/5243 exposed), almost all cases were identified in neuroblostma patients (NBL), who also received cisplatin 200mg/m²/cycle (26/92 NBL, 30y-CumInc = 36.4% (95%CI = 25.9-48.4), vs. 3/107 non-NBL, 30y-CumInc = 1.6% (0.4-5.6)). Concerning busulfan (n = 131/5243 exposed), all cases were identified in NBL (n = 16/63, all treated with melphalan and cisplatin) and brain tumors (n = 13/28, all with RT at inner ear ≥5Gy). The 30y-CumInc in patients with RT at inner ear ≥5Gy was 7.4% (95%CI = 5.7-9.6) and 39.8% (22.5-60.0) respectively with and without busulfan. Conclusions: RT at inner ear has significant deleterious impact on audition, with cumulative incidence still worsening > 30years after RT, and with likely potentiation by busulfan. The deleterious effect of melphalan was related to previous treatment with cisplatin, either by interaction between these drugs, or by the high cisplatin dose by cycle used in NBL.

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